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Morbidity and Mortality Weekly Report May 28, 2010 / Vol. 59 U.S. Medical Eligibility Criteria for
Contraceptive Use, 2010
Adapted from the World Health Organization
Medical Eligibility Criteria for Contraceptive Use, 4th edition
department of health and human services Centers for Disease Control and Prevention Early Release
The MMWR series of publications is published by the Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services, Atlanta, GA 30333.
Suggested Citation: Centers for Disease Control and Prevention.
[Title]. MMWR Early Release 2010;59[Date]:[inclusive page numbers].
Centers for Disease Control and Prevention
Thomas R. Frieden, MD, MPH Peter A. Briss, MD, MPH Acting Associate Director for Science James W. Stephens, PhD Office of the Associate Director for Science Stephen B. Thacker, MD, MSc A. Summary of Changes from WHO MEC to U.S. MEC . 7 Deputy Director for Surveillance, Epidemiology, and Laboratory Services B. Combined Hormonal Contraceptives . 11 Editorial and Production Staff
C. Progestin-Only Contraceptives . 34 Frederic E. Shaw, MD, JD D. Emergency Contraceptive Pills . 50 Editor, MMWR Series E. Intrauterine Devices . 52 Christine G. Casey, MD Deputy Editor, MMWR Series F. Copper IUDs for Emergency Contraception. 64 Teresa F. Rutledge G. Barrier Methods . 65 Managing Editor, MMWR Series H. Fertility Awareness–Based Methods . 71 Lead Technical Writer-Editor I. Lactational Amenorrhea Method . 73 Karen L. Foster, MA J. Coitus Interruptus (Withdrawal) . 74 Project Editor K. Sterilization . 75 Lead Visual Information Specialist L. Summary of Hormonal Contraceptives and IUDs. 76 M. Potential Drug Interactions: Hormonal Contraceptives Stephen R. Spriggs and Antiretroviral Drugs . 82 Visual Information Specialists Abbreviations and Acronyms . 85 Quang M. Doan, MBA Participants . 86 Information Technology Specialists William L. Roper, MD, MPH, Chapel Hill, NC, Chairman Virginia A. Caine, MD, Indianapolis, IN Jonathan E. Fielding, MD, MPH, MBA, Los Angeles, CA David W. Fleming, MD, Seattle, WA William E. Halperin, MD, DrPH, MPH, Newark, NJ King K. Holmes, MD, PhD, Seattle, WA Deborah Holtzman, PhD, Atlanta, GA John K. Iglehart, Bethesda, MD Dennis G. Maki, MD, Madison, WI Patricia Quinlisk, MD, MPH, Des Moines, IA Patrick L. Remington, MD, MPH, Madison, WI Barbara K. Rimer, DrPH, Chapel Hill, NC John V. Rullan, MD, MPH, San Juan, PR William Schaffner, MD, Nashville, TN Anne Schuchat, MD, Atlanta, GA Dixie E. Snider, MD, MPH, Atlanta, GA John W. Ward, MD, Atlanta, GA Early Release
U S. Medical Eligibility Criteria for Contraceptive Use, 2010
Adapted from the World Health Organization Medical Eligibility Criteria
for Contraceptive Use, 4th edition
Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion CDC created U.S. Medical Eligibility Criteria for Contraceptive Use, 2010, from guidance developed by the World Health Organization (WHO) and finalized the recommendations after consultation with a group of health professionals who met in Atlanta, Georgia, during February 2009. This guidance comprises recommendations for the use of specific contraceptive methods by women and men who have certain characteristics or medical conditions. The majority of the U.S. guidance does not differ from the WHO guidance and covers >60 characteristics or medical conditions. However, some WHO recommendations were modified for use in the United States, including recommendations about contraceptive use for women with venous thromboembolism, valvular heart disease, ovarian cancer, and uterine fibroids and for postpartum and breastfeeding women. Recommendations were added to the U.S. guidance for women with rheumatoid arthritis, history of bariatric surgery, peripartum cardiomyopathy, endometrial hyperplasia, inflammatory bowel disease, and solid organ transplantation. The recommendations in this document are intended to assist health-care providers when they counsel women, men, and couples about contraceptive method choice. Although these recommendations are meant to serve as a source of clinical guidance, health-care providers should always consider the individual clinical circumstances of each person seeking family planning services. programs, and the scientific community as a reference when they develop family planning guidance at the country or pro- In 1996, the World Health Organization (WHO) pub- gram level. The United Kingdom is one example of a country lished the first edition of the Medical Eligibility Criteria for that has adapted the WHO MEC for its own use (2).
Contraceptive Use (MEC), which gave evidence-based guidance CDC undertook a formal process to adapt the WHO MEC on the safety of contraceptive method use for women and at this time because the fourth edition of the WHO guidance is men worldwide who had specific characteristics and medical unlikely to undergo major revisions in the near future. Although conditions. Since that time, WHO has regularly updated its the WHO guidance is already available in the United States guidance on the basis of new evidence, and the WHO MEC through inclusion in textbooks, use by professional organizations, is now in its fourth edition (1).
and incorporation into training programs, the adaptation of the CDC, through close collaboration with WHO, has con- guidance ensures its appropriateness for use in the United States tributed substantially during the last 15 years to creation of and allows for further dissemination and implementation among WHO's global family planning guidance, which includes four U.S. health-care providers. Most of the U.S. guidance does not documents: the medical eligibility criteria for contraceptive differ from the WHO guidance and covers approximately 60 char- use, the selected practice recommendations for contraceptive acteristics or medical conditions. However, several changes have use, a decision-making tool for clients and providers, and a been made, including adaptations of selected WHO recommenda- global family planning handbook. This WHO guidance has tions, addition of recommendations for new medical conditions, been based on the best available scientific evidence, and CDC and removal of recommendations for contraceptive methods not has served as the lead for establishing that evidence base and currently available in the United States (Appendix A).
presenting the evidence to WHO for use during its expert This document contains recommendations for health-care working group meetings to create and update the guidance.
providers for the safe use of contraceptive methods by women WHO has always intended for its global guidance to be used and men with various characteristics and medical conditions. It is by local or regional policy makers, managers of family planning intended to assist health-care providers when they counsel women, men, and couples about contraceptive method choice. These Corresponding preparer: Kathryn M. Curtis, PhD, Division of
recommendations are meant to be a source of clinical guidance; Reproductive Health, CDC, MS K-34, 4770 Buford Highway NE, Atlanta, GA 30341; Telephone 770-488-6397; Fax: 770-488-6391; health-care providers should always consider the individual E-mail [email protected] clinical circumstances of each person seeking family planning Early Release
May 28, 2010
or theoretical considerations was obtained when direct evidence was not available. CDC conducted systematic reviews follow- The process for adapting the WHO MEC for the United ing standard guidelines (3,4), included thorough searches of States comprised four major steps: 1) determination of the PubMed and other databases of the scientific literature, and scope of and process for the adaptation, including a small used the U.S. Preventive Services Task Force system to grade meeting; 2) preparation and peer review of systematic reviews the strength and quality of the evidence (5). Each systematic of the evidence to be used for the adaptation; 3) organization review was peer-reviewed by two or three experts before being of a larger meeting to examine the evidence and provide input used in the adaptation process. These systematic reviews have on the recommendations; and 4) finalization of the recom- been submitted for publication in peer-reviewed journals.
mendations by CDC.
For most recommendations in this document, a limited In June 2008, CDC held a 2-day meeting of eight key number of studies address the use of a specific contraceptive partners and U.S. family planning experts to determine the method by women with a specific condition. Therefore, within scope of and process for a U.S. adaptation of the WHO MEC. the WHO guidance, as well as with this U.S. adaptation of Participants were family planning providers, who also had the guidance, most of the decisions about medical eligibility expertise in conducting research on contraceptive safety and criteria were often necessarily based on 1) extrapolations from translating research evidence into guidance. WHO guidance is studies that primarily included healthy women, 2) theoretical used widely around the world, including in the United States, considerations about risks and benefits, and 3) expert opinion. and contains approximately 1,800 separate recommendations. Evidence was particularly limited for newer contraceptive In most cases, the evidence base would be the same for the methods. The total body of evidence for each recommendation U.S. and the WHO recommendation, and—because of the included evidence based on direct studies or observations of extensive collaboration between WHO and CDC in creating the contraceptive method used by women (or men) with the the international guidance—the process for determining the condition and may have included 1) evidence derived from recommendations also would be the same. Therefore, CDC effects of the contraceptive method used by women (or men) determined that the global guidance also should be the U.S. without the condition and 2) indirect evidence or theoretical guidance, except when a compelling reason existed for adap- concerns based on studies of suitable animal models, human tation, and that CDC would accept the majority of WHO laboratory studies, or analogous clinical situations.
guidance for use in the United States.
In February 2009, CDC held a meeting of 31 experts who During the June 2008 meeting, CDC identified specific were invited to provide their individual perspective on the WHO recommendations for which a compelling reason scientific evidence presented and the discussions on poten- existed to consider modification for the United States because tial recommendations that followed. This group included of the availability of new scientific evidence or the context in obstetricians/gynecologists, pediatricians, family physicians, which family planning services are provided in the United nurse-midwives, nurse practitioners, epidemiologists, and States. CDC also identified areas in which WHO guidance others with expertise in contraceptive safety and provision. was inconsistent with current U.S. practice by contacting For each topic discussed, the evidence from the systematic numerous professional and service organizations and individual review was presented; for most of the topics, an expert in the providers. In addition, CDC assessed the need for adding rec- ommendations for medical conditions not currently included in the WHO MEC. Through this process, a list was developed BOX 1. Categories of medical eligibility criteria for
contraceptive use
of existing WHO recommendations to consider adapting and new medical conditions to consider adding to the guidance.
1 = A condition for which there is no restriction for A systematic review of the scientific evidence was conducted the use of the contraceptive method.
for each of the WHO recommendations considered for adap- 2 = A condition for which the advantages of using tation and for each of the medical conditions considered for the method generally outweigh the theoretical addition to the guidance. The purpose of these systematic or proven risks.
reviews was to identify direct evidence about the safety of 3 = A condition for which the theoretical or proven contraceptive method use by women (or men) with selected risks usually outweigh the advantages of using conditions (e.g., risk for disease progression or other adverse health effects in women with rheumatoid arthritis who use 4 = A condition that represents an unacceptable combined oral contraceptives). Information about indirect health risk if the contraceptive method is used.
evidence (e.g., evidence from healthy women or animal studies) Early Release
specific medical condition (e.g., rheumatoid arthritis) also gave smokes <15 cigarettes per day, the use of COCs usual y is a brief presentation on the condition and specific issues about not recommended unless other methods are not available or contraceptive safety. CDC gathered input from the experts acceptable to her (Category 3). A woman aged ≥35 years who during the meeting and finalized the recommendations in smokes ≥15 cigarettes per day should not use COCs because this document. CDC plans to develop a research agenda to of unacceptable health risks, primarily the risk for myocardial address topics identified during the meeting that need further infarction and stroke (Category 4). The programmatic implica- tions of these categories may depend on the circumstances of particular professional or service organizations (e.g., in some How to Use this Document
settings, a Category 3 may mean that special consultation is These recommendations are intended to help health-care pro- The recommendations address medical eligibility criteria for viders determine the safe use of contraceptive methods among the initiation and continued use of all methods evaluated. The women and men with various characteristics and medical con- issue of continuation criteria is clinically relevant whenever a ditions. Providers also can use the synthesis of information in woman develops the condition while she is using the method. these recommendations when consulting with women, men, When the categories differ for initiation and continuation, and couples about their selection of contraceptive methods. these differences are noted in the columns Initiation and The tables in this document include recommendations for the Continuation. Where Initiation and Continuation are not use of contraceptive methods by women and men with par- denoted, the category is the same for initiation and continu- ticular characteristics or medical conditions. Each condition ation of use.
was defined as representing either an individual's characteris- On the basis of this classification system, the eligibility crite- tics (e.g., age, history of pregnancy) or a known preexisting ria for initiating and continuing use of a specific contraceptive medical/pathologic condition (e.g., diabetes and hypertension). method are presented in tables (Appendices A–M). In these The recommendations refer to contraceptive methods being tables, the first column indicates the condition. Several condi- used for contraceptive purposes; the recommendations do tions were divided into subconditions to differentiate between not consider the use of contraceptive methods for treatment varying types or severity of the condition. The second column of medical conditions because the eligibility criteria in these classifies the condition for initiation and/or continuation into cases may differ. The conditions affecting eligibility for the Category 1, 2, 3, or 4. For some conditions, the numeric clas- use of each contraceptive method were classified under one of sification does not adequately capture the recommendation; four categories (Box 1).
in this case, the third column clarifies the numeric category. Using the Categories in Practice
These clarifications were determined during the discussions of the scientific evidence and the numeric classification and are Health-care providers can use these categories when assessing considered a necessary element of the recommendation. The the safety of contraceptive method use for women and men third column also summarizes the evidence for the recom- with specific medical conditions or characteristics. Category mendation, where evidence exists. The recommendations for 1 comprises conditions for which no restrictions exist for which no evidence is cited are based on expert opinion from use of the contraceptive method. Classification of a method/ either the WHO or U.S. expert working group meetings and condition as Category 2 indicates the method generally can may be based on evidence from sources other than systematic be used, but careful follow-up may be required. For a method/ reviews and presented at those meetings. For selected recom- condition classified as Category 3, use of that method usually mendations, additional comments appear in the third column is not recommended unless other more appropriate methods and generally come from the WHO or the U.S. expert working are not available or acceptable. The severity of the condition group participants.
and the availability, practicality, and acceptability of alternative methods should be taken into account, and careful follow-up Recommendations for Use of
will be required. Hence, provision of a method to a woman with a condition classified as Category 3 requires careful clinical judgement and access to clinical services. Category 4 The classifications for whether women with certain medical comprises conditions that represent an unacceptable health conditions or characteristics can use specific contraceptive risk if the method is used. For example, a smoker aged <35 methods are provided for combined hormonal contracep- years generally can use combined oral contraceptives (COCs) tive methods, including low-dose (containing ≤35 μg ethi- (Category 2). However, for a woman aged ≥35 years who nyl estradiol) combined oral contraceptive pil s, combined Early Release
May 28, 2010
hormonal patch, and combined vaginal ring (Appendix B); Contraceptive Method Effectiveness
progestin-only contraceptive methods, including progestin- only pills, depot medroxyprogesterone acetate injections, and Contraceptive method effectiveness is critically important etonogestrel implants (Appendix C); emergency contraceptive in minimizing the risk for unintended pregnancy, particularly pills (Appendix D); intrauterine contraception, including the among women for whom an unintended pregnancy would copper intrauterine device (IUD) and the levonorgestrel IUD pose additional health risks. The effectiveness of contraceptive (Appendix E); use of copper IUDs for emergency contracep- methods depends both on the inherent effectiveness of the tion (Appendix F); barrier contraceptive methods, including method itself and on how consistently and correctly it is used male and female condoms, spermicides, diaphragm with (Table 1). Methods that depend on consistent and correct use spermicide, and cervical cap (Appendix G); fertility awareness- have a wide range of effectiveness.
based methods (Appendix H); lactational amenorrhea method (Appendix I); coitus interruptus (Appendix J); and female Unintended Pregnancy and Increased
and male sterilization (Appendix K). Tables at the end of the Health Risk
document summarize the classifications for the hormonal and For women with conditions that may make unintended intrauterine methods (Appendix L) and the evidence about pregnancy an unacceptable health risk, long-acting, highly potential drug interactions between hormonal contraceptives effective contraceptive methods may be the best choice (Table and antiretroviral therapies (Appendix M).
1). Women with these conditions should be advised that sole use of barrier methods for contraception and behavior-based Contraceptive Method Choice
methods of contraception may not be the most appropriate Many elements need to be considered by women, men, or choice because of their relatively higher typical-use rates of couples at any given point in their lifetimes when choosing failure (Table 1). Conditions included in the U.S. MEC for the most appropriate contraceptive method. These elements which unintended pregnancy presents an unacceptable health include safety, effectiveness, availability (including accessibil- risk are identified throughout the document (Box 2).
ity and affordability), and acceptability. The guidance in this document focuses primarily on the safety of a given contra- Keeping Guidance Up to Date
ceptive method for a person with a particular characteristic or medical condition. Therefore, the classification of Category 1 As with any evidence-based guidance document, a key chal- means that the method can be used in that circumstance with lenge is keeping the recommendations up to date as new scien- no restrictions with regard to safety but does not necessarily tific evidence becomes available. CDC will continue to work imply that the method is the best choice for that person; other with WHO to identify and assess all new relevant evidence factors, such as effectiveness, availability, and acceptability, may and to determine whether changes to the recommendations play a key role in determining the most appropriate choice. are warranted (4). In most cases, the U.S. MEC wil fol ow any Voluntary informed choice of contraceptive methods is an updates in the WHO guidance, which typically occur every essential guiding principle, and contraceptive counseling, 3–4 years (or sooner if warranted by new data). However, where applicable, may be an important contributor to the CDC will review any WHO updates for their application in successful use of contraceptive methods.
the United States. CDC also will identify and assess any new In choosing a method of contraception, the risk for sexual y literature for the recommendations and medical conditions that transmitted infections (STIs), including human immunodefi- are not included in the WHO guidance. CDC wil completely ciency virus (HIV), also must be considered. Although hormonal review the U.S. MEC every 3–4 years as well. Updates to the contraceptives and IUDs are highly effective at preventing guidance will appear on the CDC U.S. MEC w pregnancy, they do not protect against STIs. Consistent and correct use of the male latex condom reduces the risk for STIs (6). When a male condom cannot be used properly for infection prevention, a female condom should be considered (7). Women who use contraceptive methods other than condoms should be This report is based in part on the work of the Promoting Family counseled about the use of condoms and the risk for STIs (7). Planning Team, Department of Reproductive Health and Research, Additional information about prevention and treatment of STIs World Health Organization, and its development of the WHO is available from CDC's Sexually Transmitted Diseases Treatment Medical Eligibility Criteria for Contraceptive Use, 4th edition. Early Release
TABLE 1. Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of
perfect use of contraception and the percentage continuing use at the end of the first year — United States
Women experiencing an unintended pregnancy
within the first year of use
Women continuing use at 1 year§
Typical use*
Fertility awareness–based methods Standard Days method†† TwoDay method™†† Ovulation method†† Nulliparous women Female (Reality®) Combined pill and progestin-only pill Intrauterine device ParaGard® (copper T) Mirena® (LNG-IUS) Female sterilization Male sterilization Emergency contraceptive pills*** Lactational amenorrhea methods††† Adapted from Trussell J. Contraceptive efficacy. In Hatcher RA, Trussell J, Nelson AL, Cates W, Stewart FH, Kowal D. Contraceptive technology. 19th revised
ed. New York, NY: Ardent Media; 2007.
* Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an unintended pregnancy during the first year if they do not stop use for any other reason. Estimates of the probability of pregnancy during the first year of typical use for spermicides, with- drawal, fertility awareness-based methods, the diaphragm, the male condom, the pill, and Depo-Provera are taken from the 1995 National Survey of Family Growth corrected for underreporting of abortion; see the text for the derivation of estimates for the other methods.
† Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an unintended pregnancy during the first year if they do not stop use for any other reason. See the text for the derivation of the estimate for each method.
§ Among couples attempting to avoid pregnancy, the percentage who continue to use a method for 1 year.
¶ The percentages becoming pregnant in the typical use and perfect use columns are based on data from populations where contraception is not used and from women who cease using contraception to become pregnant. Of these, approximately 89% become pregnant within 1 year. This estimate was lowered slightly (to 85%) to represent the percentage who would become pregnant within 1 year among women now relying on reversible methods of contraception if they abandoned contraception altogether.
** Foams, creams, gels, vaginal suppositories, and vaginal film.
†† The TwoDay and Ovulation methods are based on evaluation of cervical mucus. The Standard Days method avoids intercourse on cycle days 8–19.
§§ With spermicidal cream or jelly.
¶¶ Without spermicides.
*** Treatment initiated within 72 hours after unprotected intercourse reduces the risk for pregnancy by at least 75%. The treatment schedule is 1 dose within 120 hours after unprotected intercourse and a second dose 12 hours after the first dose. Both doses of Plan B can be taken at the same time. Plan B (1 dose is 1 white pill) is the only dedicated product specifically marketed for emergency contraception. The Food and Drug Administration has in addition declared the following 22 brands of oral contraceptives to be safe and effective for emergency contraception: Ogestrel or Ovral (1 dose is 2 white pills); Levlen or Nordette (1 dose is 4 light-orange pills); Cryselle, Levora, Low-Ogestrel, Lo/Ovral, or Quasence (1 dose is 4 white pills); Tri-Levlen or Triphasil (1 dose is 4 yellow pills); Jolessa, Portia, Seasonale, or Trivora (1 dose is 4 pink pills); Seasonique (1 dose is 4 light blue-green pills); Empresse (1 dose is 4 orange pills); Alesse, Lessina, or Levlite (1 dose is 5 pink pills); Aviane (1 dose is 5 orange pills); and Lutera (1 dose is 5 white pills).
††† Lactational amenorrhea method is a highly effective temporary method of contraception. However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeding is reduced, bottle feeds are introduced, or the baby reaches 6 months of age.
Early Release
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BOX 2. Conditions associated with increased risk for adverse
health events as a result of unintended pregnancy
1. WHO. Medical eligibility criteria for contraceptive use. 4th ed. Geneva: WHO; 2009. Available 2. Faculty of Family Planning and Reproductive Health Care, Royal Col ege Complicated valvular heart disease of Obstetricians and Gynecologists. UK medical eligibility criteria for contraceptive use, 2005–2006. London: Faculty of Family Planning and Diabetes: insulin-dependent; with nephropathy/ Reproductive Health Care, 2006.
retinopathy/neuropathy or other vascular disease; or 3. Stroup DF, Berlin JA, Morton SC, et al. Meta-analysis of observational of >20 years' duration studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA Endometrial or ovarian cancer 4. Mohllajee AP, Curtis KM, Flanagan RG, et al. Keeping up with evidence a new system for WHO's evidence-based family planning guidance. Am Hypertension (systolic >160 mm Hg or diastolic J Prev Med 2005;28:483–90.
5. Harris RP, Helfand M, Woolf SH, et al. Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med History of bariatric surgery within the past 2 years 6. CDC. Condom fact sheet in brief. Available at Ischemic heart disease 7. CDC. Sexual y transmitted diseases treatment guidelines, 2006. MMWR 2006;55(RR No. 11).
Malignant gestational trophoblastic diseaseMalignant liver tumors (hepatoma) and hepatocellular carcinoma of the liver Peripartum cardiomyopathySchistosomiasis with fibrosis of the liverSevere (decompensated) cirrhosisSickle cell diseaseSolid organ transplantation within the past 2 yearsStrokeSystemic lupus erythematosusThrombogenic mutationsTuberculosis Early Release
Appendix A
Summary of Changes to the World Health Organization Medical Eligibility
Criteria for Contraceptive Use, 4th Edition, to Create the U.S. Medical
Eligibility Criteria for Contraceptive Use, 2010
The classification additions, deletions, and modifications classification changed for ≥1 methods or the condition descrip- from the World Health Organization (WHO) Medical tion underwent a major modification, WHO conditions and Eligibility Criteria for Contraceptive Use, 4th Edition, are recommendations appear in curly brackets.
summarized below (Tables 1–3). For conditions for which BOX. Categories for Classifying Hormonal Contraceptives and Intrauterine Devices
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE 1. Summary of changes in classifications from WHO Medical Eligibility Criteria for Contraceptive Use, 4th edition*†
Condition
The US Department of Health a. <1 mo postpartum {WHO: and Human Services recom- <6 wks postpartum} mends that infants be exclusively b. 1 mo to <6 mos {WHO: ≥6 breastfed during the first 4–6 wks to <6 mos postpartum} months of life, preferably for a full 6 months. Ideally, breastfeed- ing should continue through the first year of life (1). {Not included Postpartum (in breastfeeding
or nonbreastfeeding women),
including post caesarean
a. <10 min after delivery of the placenta {WHO: <48 hrs, including insertion im- mediately after delivery of b. 10 min after delivery of the placenta to <4 wks {WHO: ≥48 hrs to <4 wks} Deep venous thrombosis
(DVT)/pulmonary embolism
a. History of DVT/PE, not on anticoagulant therapy ii. Lower risk for recurrent DVT/PE (no risk factors) c. DVT/PE and established on anticoagulant therapy for at Early Release
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TABLE 1. (Continued) Summary of changes in classifications from WHO Medical Eligibility Criteria for Contraceptive Use,
i. Higher risk for recurrent DVT/PE (≥1 risk factors) • Known thrombophilia, antiphospholipid • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), melanoma skin cancer • History of recurrent ii. Lower risk for recurrent Women on anticoagulant therapy DVT/PE (no risk factors) are at risk for gynecologic com- plications of therapy such as hemorrhagic ovarian cysts and severe menorrhagia. Hormonal contraceptive methods can be of benefit in preventing or treating these complications. When a contraceptive method is used as a therapy, rather than solely to prevent pregnancy, the risk/ benefit ratio may be different and should be considered on a case- by-case basis. {Not included in Valvular heart disease
b. Complicated¶ (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial 1 {Initiation = 3, 1 {Initiation = 3, Continuation = 2} Continuation = 2} 2 {1 if no uterine 2 {1 if no uterine distortion and 4 if distortion and 4 if uterine distortion uterine distortion is * For conditions for which classification changed for ≥1 methods or the condition description underwent a major modification, WHO conditions and recom- mendations appear in curly brackets.
† Abbreviations: WHO = World Health Organization; COC = combined oral contraceptive; P = combined hormonal contraceptive patch; R = combined hormonal vaginal ring; POP = progestin-only pill; DMPA = depot medroxyprogesterone acetate; LNG-IUD = levonorgestrel-releasing intrauterine device; Cu-IUD = copper intrauterine device; DVT = deep venous thrombosis; PE = pulmonary embolism; VTE = venous thromboembolism.
§ Consult the clarification column for this classification. ¶ Condition that exposes a women to increased risk as a result of unintended pregnancy.
Early Release
TABLE 2. Summary of recommendations for medical conditions added to the U.S. Medical Eligibility Criteria for Contraceptive Use*
Condition
COC/P/R POP DMPA Implants
History of bariatric surgery†
a. Restrictive procedures: decrease storage
capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, laparoscopic sleeve b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass, biliopancreatic diversion) Peripartum cardiomyopathy†
a. Normal or mildly impaired cardiac
function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (2) b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (2) a. On immunosuppressive therapy DMPA use among women on long-term corti-costeroid therapy with a history of, or risk factors for, nontraumatic fractures is classified as Cat-egory 3. Otherwise, DMPA use for women with rheumatoid arthritis is classified as Category 2.
b. Not on immunosuppressive therapy Inflammatory bowel disease (IBD)
For women with mild IBD, with no other risk (ulcerative colitis, Crohn disease) factors for VTE, the benefits of COC/P/R use generally outweigh the risks (Category 2). However, for women with IBD with increased risk for VTE (e.g., those with active or extensive disease, surgery, immobilization, corticosteroid use, vitamin deficiencies, fluid depletion), the risks for COC/P/R use generally outweigh the benefits (Category 3).
Solid organ transplantation†
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft Women with Budd-Chiari syndrome should not use COC/P/R because of the increased risk for thrombosis.
* Abbreviations: COC = combined oral contraceptive; P = combined hormonal contraceptive patch; R = combined hormonal vaginal ring: POP = progestin-only pill; DMPA = depot medroxyprogesterone acetate; LNG-IUD = levonorgestrel-releasing intrauterine device; Cu-IUD = copper intrauterine device; IBD = inflammatory bowel disease; VTE = venous
thromboembolism.
† Condition that exposes a women to increased risk as a result of unintended pregnancy.
§ Consult the clarification column for this classification.
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TABLE 3. Summary of additional changes to the U.S. Medical Eligibility Criteria for Contraceptive Use
Condition/Contraceptive method
Emergency contraceptive pills History of bariatric surgery, rheumatoid arthritis, inflammatory bowel disease, and solid organ transplantation were added to Appendix D and given a Category 1. For 6 conditions—history of bariatric surgery, peripartum cardiomyopathy, rheumatoid arthritis, endometrial hyperplasia, inflammatory bowel disease, and solid organ transplantation—the barrier methods are classified as Category 1.
In general, no medical conditions would absolutely restrict a person's eligibility for sterilization. Recommendations from the World Health Organization (WHO) Medical Eligibility Criteria for Contraceptive Use about specific settings and surgical procedures for sterilization are not included here. The guidance has been replaced with general text on sterilization.
Other deleted items Guidance for combined injectables, levonorgestrel implants, and norethisterone enanthate has been re- moved because these methods are not currently available in the United States.
Guidance for "blood pressure measurement unavailable" and "history of hypertension, where blood pressure CANNOT be evaluated (including hypertension in pregnancy)" has been removed.
Unintended pregnancy and increased The following conditions have been added to the WHO list of conditions that expose a woman to increased risk as a result of unintended pregnancy: history of bariatric surgery within the past 2 years, peripartum car- diomyopathy, and receiving a solid organ transplant within 2 years.
1. Office on Women's Health, US Department of Health and Human 2. The Criteria Committee of the New York Heart Association. Nomenclature Services. HHS blueprint for action on breastfeeding. Washington, DC: and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. US Department of Health and Human Services, Office on Women's Boston, MA: Little, Brown & Co; 1994.
Health; 2000.
Early Release
Appendix B
Classifications for Combined Hormonal Contraceptives
Combined hormonal contraceptives (CHCs) include low- and pharmacokinetic profiles to COCs with similar hormone dose (containing ≤35 μg ethinyl estradiol [EE]) combined oral formulations (1–33). Pending further studies, the evidence contraceptives (COCs), the combined hormonal patch, and available for recommendations about COCs applies to the the combined vaginal ring. The combined hormonal patch and recommendations for the combined hormonal patch and vagi- vaginal ring are relatively new contraceptive methods. Limited nal ring. Therefore, the patch and ring should have the same information is available about the safety of these methods categories (Box) as COCs, except where noted. The assigned among women with specific medical conditions. Moreover, categories should, therefore, be considered a preliminary, best epidemiologic data on the long-term effects of the combined judgement, which wil be reevaluated as new data become hormonal patch and the vaginal ring were not available for available. CHCs do not protect against sexually transmitted review. Evidence indicates that the combined hormonal patch infections (STIs) or human immunodeficiency virus (HIV).
and the combined vaginal ring provide comparable safety BOX. Categories for Classifying Combined Hormonal Contraceptives
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Personal Characteristics and Reproductive History
Clarification: Use of COCs, P, or R is not required. There is no known harm to the woman, the course of
her pregnancy, or the fetus if COCs, P, or R are inadvertently used during pregnancy.
a. Menarche to <40 yrs Evidence: Adolescents using 20 μg EE-containing COCs have lower BMD than do nonusers, and higher
dose-containing COCs have little to no effect. (34–41). In premenopausal adult women, COC use has little to no effect on bone health while appearing to preserve bone mass in perimenopausal women (26,42–90). Postmenopausal women who have ever used COCs have similar BMD to postmenopausal women who have never used COCs (54,58,68,81,91–110). BMD in adolescent or premenopausal women may not ac-curately predict postmenopausal fracture risk (109,111–122).
Comment: The risk for cardiovascular disease increases with age and might increase with CHC use. In the
absence of other adverse clinical conditions, CHCs can be used until menopause.
Clarification: The U.S. Department of Health and Human Services recommends that infants be exclusively
a. <1 mo postpartum breastfed during the first 4–6 months of life, preferably for a full 6 months. Ideally, breastfeeding should b. 1 mo to <6 mos postpartum continue through the first year of life (123).
c. ≥6 mos postpartum Evidence: Clinical studies demonstrate conflicting results about effects on milk volume in women exposed
to COCs during lactation; no consistent effect on infant weight has been reported. Adverse health outcomes
or manifestations of exogenous estrogen in infants exposed to CHCs through breast milk have not been
demonstrated (124–133). In general, these studies are of poor quality, lack standard definitions of breast-
feeding or outcome measures, and have not included premature or ill infants. Theoretical concerns about
effects of CHCs on breast milk production are greater in the early postpartum period when milk flow is being
established.
Early Release
May 28, 2010
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Postpartum (in nonbreastfeeding
women)
Comment: Theoretical concern exists about the association between CHC use up to 3 weeks postpartum
and risk for thrombosis in the mother. Blood coagulation and fibrinolysis are essentially normalized by 3 weeks postpartum.
Clarification: COCs, P, or R may be started immediately postabortion.
a. First trimester Evidence: Women who started taking COCs immediately after first trimester medical or surgical abortion
b. Second trimester did not experience more side effects or adverse vaginal bleeding outcomes or clinically significant changes c. Immediate postseptic abortion in coagulation parameters than did women who used a placebo, an IUD, a nonhormonal contraceptive method, or delayed COC initiation (134–140). Limited evidence on women using the ring immediately after first trimester medical or surgical abortion found no serious adverse events and no infection related to use of the combined vaginal contraceptive ring during 3 cycles of follow-up postabortion (141).
Past ectopic pregnancy
Comment: The risk for future ectopic pregnancy is increased among women who have had an ectopic
pregnancy in the past. CHCs protect against pregnancy in general, including ectopic gestation.
History of pelvic surgery
a. Age <35 yrs Evidence: COC users who smoked were at increased risk for cardiovascular diseases, especially myocar-
dial infarction, than those who did not smoke. Studies also showed an increased risk for myocardial infarc- i. <15 Cigarettes/day tion with increasing number of cigarettes smoked per day (142–153).
ii. ≥15 Cigarettes/day a. ≥30 kg/m2 BMI Evidence: Obese women who use COCs are more likely than obese women who do not use COCs to
b. Menarche to <18 yrs and experience VTE. The absolute risk for VTE in healthy women of reproductive age is small. Limited evidence suggests that obese women who use COCs do not have a higher risk for acute myocardial infarction or stroke than do obese nonusers (147,153–159). Limited evidence is inconsistent about whether COC ef-fectiveness varies by body weight or BMI (160–165). Limited evidence suggests obese women are no more likely to gain weight after 3 cycles of the vaginal ring or COC than overweight or normal weight women. A similar weight gain during the 3 months was noted between the COC group and the vaginal ring group across all BMI categories (166). The effectiveness of the patch decreased among women who weighed >90 kg; however, no association was found between pregnancy risk and BMI (18).
History of bariatric surgery§
a. Restrictive procedures: decrease Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives
storage capacity of the stomach among women who underwent laparoscopic placement of an adjustable gastric band (167).
(vertical banded gastroplasty, laparoscopic adjustable gastric band, laparoscopic sleeve gastrectomy) b. Malabsorptive procedures: decrease Evidence: Limited evidence demonstrated no substantial decrease in effectiveness of oral contraceptives
absorption of nutrients and calories among women who underwent a biliopancreatic diversion (168); however, evidence from pharmacokinetic by shortening the functional length of studies reported conflicting results of oral contraceptive effectiveness among women who underwent a the small intestine (Roux-en-Y gas- jejunoileal bypass (169,170).
tric bypass, biliopancreatic diversion) Comment: Bariatric surgical procedures involving a malabsorptive component have the potential to de-
crease oral contraceptive effectiveness, perhaps further decreased by postoperative complications, such as
long-term diarrhea and/or vomiting.
Multiple risk factors for arte-
Clarification: When a woman has multiple major risk factors, any of which alone would substantially
rial cardiovascular disease (such
increase her risk for cardiovascular disease, use of COCs, P, or R might increase her risk to an unaccept- as older age, smoking, diabetes, and able level. However, a simple addition of categories for multiple risk factors is not intended; for example, a combination of two risk factors assigned a category 2 might not necessarily warrant a higher category.
Hypertension
For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist,
risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
a. Adequately controlled hypertension Clarification: Women adequately treated for hypertension are at reduced risk for acute myocardial
infarction and stroke compared with untreated women. Although no data exist, COC, P, or R users with
adequately controlled and monitored hypertension should be at reduced risk for acute myocardial infarction
and stroke compared with untreated hypertensive COC, P, or R users.
b. Elevated blood pressure levels (properly taken measurements) Early Release
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
i. Systolic 140–159 mm Hg or Evidence: Among women with hypertension, COC users were at higher risk than nonusers for
diastolic 90–99 mm Hg stroke, acute myocardial infarction, and peripheral arterial disease (142,144,151–153,155,171–186). ii. Systolic ≥160 mm Hg or diastolic Discontinuation of COCs in women with hypertension might improve blood pressure control (187).
c. Vascular disease History of high blood pressure during
Evidence: Women with a history of high blood pressure in pregnancy, who also used COCs, had a
pregnancy (where current blood pres-
higher risk for myocardial infarction and VTE than did COC users who did not have a history of high blood sure is measurable and normal) pressure during pregnancy. The absolute risks for acute myocardial infarction and VTE in this population remained small (153,172,184–186,188–193).
Deep venous thrombosis (DVT)/
Pulmonary embolism (PE)
a. History of DVT/PE, not on anticoagu- lant therapy i. Higher risk for recurrent DVT/PE (≥1 risk factors) • History of estrogen-associated • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no risk factors) c. DVT/PE and established on anti- coagulant therapy for at least 3 mos i. Higher risk for recurrent DVT/PE Clarification: Women on anticoagulant therapy are at risk for gynecologic complications of therapy, such
(≥1 risk factors) as hemorrhagic ovarian cysts and severe menorrhagia. Hormonal contraceptive methods can be of benefit • Known thrombophilia, including in preventing or treating these complications. When a contraceptive method is used as a therapy, rather than solely to prevent pregnancy, the risk/benefit ratio might differ and should be considered on a case-by- • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE Clarification: Women on anticoagulant therapy are at risk for gynecologic complications of therapy, such
(no risk factors) as hemorrhagic ovarian cysts and severe menorrhagia. Hormonal contraceptive methods can be of benefit in preventing or treating these complications. When a contraceptive method is used as a therapy, rather than solely to prevent pregnancy, the risk/benefit ratio may differ and should be considered on a case-by-case basis.
d. Family history (first-degree relatives) Comment: Some conditions that increase the risk for DVT/PE are heritable.
i. With prolonged immobilization ii. Without prolonged immobilization f. Minor surgery without immobilization Known thrombogenic mutations§
Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost
(e.g., factor V Leiden; prothrombin muta- of screening.
tion; protein S, protein C, and antithrom- Evidence: Among women with thrombogenic mutations, COC users had a 2-fold to 20-fold higher risk for
bin deficiencies) thrombosis than did nonusers (159,194–216).
Superficial venous thrombosis
a. Varicose veins Comment: Varicose veins are not risk factors for DVT/PE
b. Superficial thrombophlebitis Current and history of ischemic heart
Stroke§ (history of cerebrovascular
Early Release
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TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Clarification: Routine screening is not appropriate because of the rarity of the conditions and the high cost
of screening. Although some types of hyperlipidemias are risk factors for vascular disease, the category
should be assessed according to the type, its severity, and the presence of other cardiovascular risk
factors.
Valvular heart disease
b. Complicated§ (pulmonary hyperten- Comment: Among women with valvular heart disease, CHC use may further increase the risk for arterial
sion, risk for atrial fibrillation, history thrombosis; women with complicated valvular heart disease are at greatest risk.
of subacute bacterial endocarditis) a. Normal or mildly impaired car- Evidence: No direct evidence exists about the safety of COCs/P/R among women with peripartum
diac function (New York Heart cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease Association Functional Class I or II: demonstrated few cases of hypertension and transient ischemic attack in women with cardiac disease using patients with no limitation of activities COCs. No cases of heart failure were reported (218).
or patients with slight, mild limitation Comment: COCs might increase fluid retention in healthy women; fluid retention may worsen heart failure
of activity) (217) in women with peripartum cardiomyopathy. COCs might induce cardiac arrhythmias in healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
b. Moderately or severely impaired Evidence: No direct evidence exists about the safety of COCs/P/R among women with peripartum
cardiac function (New York Heart cardiomyopathy. Limited indirect evidence from noncomparative studies of women with cardiac disease Association Functional Class III or demonstrated few cases of hypertension and transient ischemic attack in women with cardiac disease using IV: patients with marked limitation of COCs. No cases of heart failure were reported (218).
activity or patients who should be at complete rest) (217) Comment: COCs might increase fluid retention in healthy women; fluid retention may worsen heart failure
in women with peripartum cardiomyopathy. COCs might induce cardiac arrhythmias in healthy women;
women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
Systemic lupus erythematosus (SLE)§
Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in the MEC should be the same for women with
SLE who present with these conditions. For all categories of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are pres-
ent; these classifications must be modified in the presence of such risk factors.
Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (219–237).
a. Positive (or unknown) antiphospho- Evidence: Antiphospholipid antibodies are associated with a higher risk for both arterial and venous throm-
b. Severe thrombocytopenia c. Immunosuppressive treatment d. None of the above a. On immunosuppressive therapy Evidence: Limited evidence shows no consistent pattern of improvement or worsening of rheumatoid arthri-
tis with use of oral contraceptives (240–245), progesterone (246), or estrogen (247).
b. Not on immunosuppressive therapy Initiation Continuation Clarification: Classification depends on accurate diagnosis of those severe headaches that are migrainous
and those headaches that are not. Any new headaches or marked changes in headaches should be evalu-ated. Classification is for women without any other risk factors for stroke. Risk for stroke increases with age, hypertension and smoking.
a. Non-migrainous (mild or severe) Evidence: Among women with migraine, women who also had aura had a higher risk for stroke than did
those without aura (248–250). Women with a history of migraine who use COCs are about 2–4 times as • Age <35 yrs likely to have an ischemic stroke as nonusers with a history of migraine (142,157,179,180,249-254).
• Age ≥35 yrs Comment: Aura is a specific focal neurologic symptom. For more information about this and other diag-
ii. With aura, at any age nostic criteria, see: Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders, 2nd ed. Cephalalgia. 2004;24(Suppl 1). Available Clarification: If a woman is taking anticonvulsants, refer to the section on drug interactions. Certain anti-
convulsants lower COC effectiveness. The extent to which P or R use is similar to COC use in this regard
remains unclear.
Early Release
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Clarification: The classification is based on data for women with selected depressive disorders. No data on
bipolar disorder or postpartum depression were available. Drug interactions potentially can occur between
certain antidepressant medications and hormonal contraceptives.
Evidence: COC use did not increase depressive symptoms in women with depression compared with base-
line or with nonusers with depression (255–264).
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy Comment: Irregular menstrual bleeding patterns are common among healthy women.
b. Heavy or prolonged bleeding (in- Clarification: Unusually heavy bleeding should raise suspicion of a serious underlying condition.
cludes regular and irregular patterns) Evidence: A Cochrane Collaboration Review identified 1 randomized controlled trial evaluating the ef-
fectiveness of COC use compared with naproxen and danazol in treating menorrhagic women. Women with
menorrhagia did not report worsening of the condition or any adverse events related to COC use (265).
Unexplained vaginal bleeding
(suspicious for serious condition)
Before evaluation Clarification: If pregnancy or an underlying pathological condition (such as pelvic malignancy) is sus-
pected, it must be evaluated and the category adjusted after evaluation.
Comment: No conditions that cause vaginal bleeding will be worsened in the short term by use of CHCs.
Evidence: A Cochrane Collaboration Review identified 1 randomized controlled trial evaluating the effec-
tiveness of COC use compared with a gonadotropin-releasing hormone analogue in treating the symptoms
of endometriosis. Women with endometriosis did not report worsening of the condition or any adverse
events related to COC use (266).
Benign ovarian tumors (including cysts)
Evidence: Risk for side effects with COC use was not higher among women with dysmenorrhea than
among women not using COCs. Some COC users had a reduction in pain and bleeding (267,268).
Gestational trophoblastic disease
a. Decreasing or undetectable β–hCG Evidence: After molar pregnancy evacuation, the balance of evidence found COC use did not increase
the risk for postmolar trophoblastic disease, and β-hCG levels regressed more rapidly in some COC users than in nonusers (269–275). Limited evidence suggests that use of COCs during chemotherapy does not b. Persistently elevated β-hCG levels or significantly affect the regression or treatment of postmolar trophoblastic disease compared with women malignant disease§ who used a nonhormonal contraceptive method or DMPA during chemotherapy (276).
Comment: Cervical ectropion is not a risk factor for cervical cancer, and restriction of CHC use is
unnecessary.
Cervical intraepithelial neoplasia
Evidence: Among women with persistent HPV infection, long-term COC use (≥5 years) might increase
the risk for carcinoma in situ and invasive carcinoma (21,277). Limited evidence on women with low-grade
squamous intraepithelial lesions found use of the vaginal ring did not worsen the condition (21).
Cervical cancer (awaiting treatment)
Comment: Theoretical concern exists that CHC use might affect prognosis of the existing disease. While
awaiting treatment, women may use CHCs. In general, treatment of this condition can render a woman
sterile.
a. Undiagnosed mass Clarification: The woman should be evaluated as early as possible.
b. Benign breast disease c. Family history of cancer Evidence: Women with breast cancer susceptibility genes (such as BRCA1 and BRCA2) have a higher
baseline risk for breast cancer than do women without these genes. The baseline risk for breast cancer is
also higher among women with a family history of breast cancer than among those who do not have such
a history. However, current evidence does not suggest that the increased risk for breast cancer among
women with either a family history of breast cancer or breast cancer susceptibility genes is modified by the
use of COCs (278–295).
d. Breast cancer§ Comment: Breast cancer is a hormonally sensitive tumor, and the prognosis for women with current or
recent breast cancer might worsen with CHC use.
ii. Past and no evidence of current disease for 5 yrs Comment: COC use reduces the risk for endometrial cancer; whether P or R use reduces the risk for
endometrial cancer is not known. While awaiting treatment, women may use COCs, P, or R. In general, treatment of this condition renders a woman sterile.
Early Release
May 28, 2010
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Comment: COC use reduces the risk for ovarian cancer; whether P or R use reduces the risk for ovarian
cancer is not known. While awaiting treatment, women may use COCs, P, or R. In general, treatment of this
condition can render a woman sterile.
Comment: COCs do not appear to cause growth of uterine fibroids, and P and R also are not expected to
cause growth.
Pelvic inflammatory disease (PID)
a. Past PID (assuming no current risk Comment: COCs might reduce the risk for PID among women with STIs but do not protect against HIV
factors for STIs) or lower genital tract STIs. Whether use of P or R reduces the risk for PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STIs.
i. With subsequent pregnancy ii. Without subsequent pregnancy a. Current purulent cervicitis or chla- mydial infection or gonorrhea b. Other STIs (excluding HIV and c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs Evidence: Evidence suggests that chlamydial cervicitis may be increased among COC users at high risk
for STIs. For other STIs, there is either evidence of no association between COC use and STI acquisition or
too limited evidence to draw any conclusions (296–376).
High risk for HIV
Evidence: The balance of the evidence suggests no association between oral contraceptive use and HIV
acquisition, although findings from studies conducted among higher risk populations have been inconsistent
(377–415).
Evidence: Most studies suggest no increased risk for HIV disease progression with hormonal contraceptive
use, as measured by changes in CD4 cell count, viral load, or survival. Studies observing that women with
HIV who use hormonal contraception have increased risks of acquiring STIs are generally consistent with
reports among uninfected women. One direct study found no association between hormonal contraceptive
use and an increased risk for HIV transmission to uninfected partners; several indirect studies reported
mixed results about whether hormonal contraception is associated with increased risk for HIV-1 DNA or
RNA shedding from the genital tract (377,416–432).
Clarification: Drug interactions may occur between hormonal contraceptives and ARV therapy; refer to the
section on drug interactions.
Evidence: Among women with uncomplicated schistosomiasis, COC use had no adverse effects on liver
function (433–439).
b. Fibrosis of liver§ (if severe, see Clarification: If a woman is taking rifampicin, refer to the section on drug interactions. Rifampicin is likely to
decrease COC effectiveness. The extent to which P or R use is similar to COC use in this regard remains a. History of gestational disease Evidence: The development of noninsulin-dependant diabetes in women with a history of gestational
diabetes is not increased by use of COCs (440–447). Likewise, lipid levels appear to be unaffected by COC
use (448–450).
b. Nonvascular disease Evidence: Among women with insulin- or noninsulin-dependent diabetes, COC use had limited effect on
i. Noninsulin-dependent daily insulin requirements and no effect on long-term diabetes control (e.g., glycosylated hemoglobin levels) ii. Insulin-dependent§ or progression to retinopathy. Changes in lipid profile and hemostatic markers were limited, and most changes remained within normal values (451–460).
c. Nephropathy/retinopathy/ Clarification: The category should be assessed according to the severity of the condition.
d. Other vascular disease or diabetes of Clarification: The category should be assessed according to the severity of the condition.
>20 yrs' duration§ Early Release
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Inflammatory bowel disease (IBD)
Clarification: For women with mild IBD and no other risk factor for VTE, the benefits of COC/P/R use
(ulcerative colitis, Crohn disease) generally outweigh the risks (Category 2). However, for women with IBD who are at increased risk for VTE (e.g., those with active or extensive disease, surgery, immobilization, corticosteroid use, vitamin deficien-cies, or fluid depletion), the risks of COC/P/R use generally outweigh the benefits (Category 3).
Evidence: Risk for disease relapse was not significantly higher among women with IBD using oral contra-
ceptives (most studies did not specify formulation) than among nonusers (461–465).
Absorption of COCs among women with mild ulcerative colitis and no or small ileal resections was similar to the absorption among healthy women (466,467). Findings might not apply to women with Crohn disease or more extensive bowel resections.
No data exist that evaluate the increased risk for VTE among women with IBD using COCs/P/R. However, women with IBD are at higher risk than unaffected women for VTE (468).
Comment: COCs, P, or R might cause a small increased risk for gallbladder disease. COCs, P, or R might
i. Treated by cholecystectomy worsen existing gallbladder disease.
ii. Medically treated History of cholestasis
a. Pregnancy-related Comment: History of pregnancy-related cholestasis might predict an increased risk for COC-related
cholestasis.
b. Past COC-related Comment: History of COC-related cholestasis predicts an increased risk with subsequent COC use.
Initiation Continuation a. Acute or flare Clarification for initiation: The category should be assessed according to the severity of the condition.
Evidence: Data suggest that in women with chronic hepatitis, COC use does not increase the rate or sever-
ity of cirrhotic fibrosis, nor does it increase the risk for hepatocellular carcinoma (469,470). For women who are carriers, COC use does not appear to trigger liver failure or severe dysfunction (471-473). Evidence is limited for COC use during active hepatitis (474).
a. Mild (compensated) b. Severe§ (decompensated) Liver tumors
Evidence: Limited direct evidence suggests that hormonal contraceptive use does not influence either
i. Focal nodular hyperplasia progression or regression of liver lesions among women with focal nodular hyperplasia (475,476).
ii. Hepatocellular adenoma§ b. Malignant§ (hepatoma) Comment: Anecdotal evidence from countries where thalassemia is prevalent indicates that COC use does
not worsen the condition.
Sickle cell disease§
Iron deficiency anemia
Comment: CHC use may decrease menstrual blood loss.
Solid Organ Transplantation
Solid organ transplantation§
a. Complicated: graft failure (acute or Evidence: Limited evidence of COC and P users indicated no overall changes in biochemical measures.
chronic), rejection, cardiac allograft However, one study reported discontinuations of COC use in 2 (8%) of 26 women as a result of serious medical complications, and in one case report, a woman developed cholestasis associated with high-dose COC use (477–480).
Clarification: Women with Budd-Chiari syndrome should not use COC/P/R because of the increased risk
for thrombosis.
Evidence: Limited evidence of COC and P users indicated no overall changes in biochemical measures.
However, one study reported discontinuations of COC use in 2 (8%) of 26 women as a result of serious
medical complications, and in one case report, a woman developed cholestasis associated with high-dose
COC use (477–480).
Early Release
May 28, 2010
TABLE. (Continued) Classifications for combined hormonal contraceptives, including pill, patch, and ring*†
Condition
Antiretroviral (ARV) therapy
Clarification: ARV drugs have the potential to either decrease or increase the bioavailability of steroid
a. Nucleoside reverse transcriptase hormones in hormonal contraceptives. Limited data (summarized in Appendix M) suggest potential drug inhibitors (NRTIs) interactions between many ARV drugs (particularly some non-NNRTIs and ritonavir-boosted protease b. Non-nucleoside reverse tran- inhibitors) and hormonal contraceptives. These interactions might alter the safety and effectiveness of both scriptase inhibitors (NNRTIs) the hormonal contraceptive and the ARV drug. Thus, if a woman on ARV treatment decides to initiate or c. Ritonavir-boosted protease inhibitors continue hormonal contraceptive use, the consistent use of condoms is recommended to both prevent HIV transmission and compensate for any possible reduction in the effectiveness of the hormonal contraceptive. When a COC is chosen, a preparation containing a minimum of 30 µg EE should be used.
Clarification: Although the interaction of certain anticonvulsants with COCs, P, or R is not harmful to
a. Certain anticonvulsants (phenytoin, women, it is likely to reduce the effectiveness of COCs, P, or R. Use of other contraceptives should be en- carbamazepine, barbiturates, primi- couraged for women who are long-term users of any of these drugs. When a COC is chosen, a preparation done, topiramate, oxcarbazepine) containing a minimum of 30 µg EE should be used.
Evidence: Use of certain anticonvulsants might decrease the effectiveness of COCs (481–484).
Clarification: The recommendation for lamotrigine applies only for situations where lamotrigine mono-
therapy is taken concurrently with COCs. Anticonvulsant treatment regimens that combine lamotrigine and
nonenzyme-inducing antiepileptic drugs (such as sodium valproate) do not interact with COCs.
Evidence: Pharmacokinetic studies show levels of lamotrigine decrease significantly during COC use
(485–489). Some women who used both COCs and lamotrigine experienced increased seizure activity in
one trial (485).
a. Broad-spectrum antibiotics Evidence: Most broad-spectrum antibiotics do not affect the contraceptive effectiveness of COCs(490–
526), P (527) or R (528).
Evidence: Studies of antifungal agents have shown no clinically significant pharmacokinetic interactions
with COCs (529–538) or R (539).
c. Antiparasitics Evidence: Studies of antiparasitic agents have shown no clinically significant pharmacokinetic interactions
with COCs (433,540–544).
d. Rifampicin or rifabutin therapy Clarification: Although the interaction of rifampicin or rifabutin therapy with COCs, P, or R is not harmful
to women, it is likely to reduce the effectiveness of COCs, P, or R. Use of other contraceptives should be
encouraged for women who are long-term users of either of these drugs. When a COC is chosen, a prepa-
ration containing a minimum of 30 µg EE should be used.
Evidence: The balance of the evidence suggests that rifampicin reduces the effectiveness of COCs
(545–560). Data on rifabutin are limited, but effects on metabolism of COCs are less than with rifampicin,
and small studies have not shown evidence of ovulation (547,554).
* Abbreviations: STI = sexually transmitted infection; HIV = human immunodeficiency virus; COC = combined oral contraceptive; P = patch; R = ring; EE = ethinyl estradiol; BMD = bone mineral density; CHC = combined hormonal contraceptive; IUD = intrauterine device; VTE = venous thromboembolism; BMI = body mass index; DVT = deep venous thrombosis; PE = pulmonary embolism; SLE = systemic lupus erythematosus; MEC = Medical Eligibility Criteria; hCG = human chorionic gonadotropin; DMPA = depot medroxyprogesterone acetate; HPV = human papillomavirus; PID = pelvic inflammatory disease; AIDS = acquired immunodeficiency syndrome; ARV = antiretroviral; IBD = inflammatory bowel disease; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor. † COCs/P/R do not protect against STI/HIV. If risk for STI/HIV (including during pregnancy or postpartum) exists, the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STI/HIV transmission.
§ Condition that exposes a woman to increased risk as a result of unintended pregnancy.
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pants. Contraception 2001;64:287–94.
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502. Friedman CI, Huneke AL, Kim MH, Powell J. The effect of ampicillin 482. Doose DR, Wang S, Padmanabhan M, et al. Effects of topiramate on oral contraceptive effectiveness. Obstet Gynecol 1980;55:33–7.
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tirazole antifungal drug [in German]. Wien Med Wochenschr 514. London BM, Lookingbill DP. Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives. Arch Dermatol 536. Sinofsky FE, Pasquale SA. The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives. Am J 515. Maggiolo F, Puricelli G, Dottorini M, et al. The effects of cipro- Obstet Gynecol 1998;178:300–4.
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518. Pil ans PI, Sparrow MJ. Pregnancy associated with a combined oral con- 539. Verhoeven CH, van den Heuvel MW, Mulders TM, Dieben TO. The traceptive and itraconazole [comment]. N Z Med J 1993;106:436.
contraceptive vaginal ring, NuvaRing, and antimycotic co-medication. 519. Scholten PC, Droppert RM, Zwinkels MG, et al. No interaction between ciprofloxacin and an oral contraceptive. Antimicrob Agents 540. Back DJ, Breckenridge AM, Grimmer SF, Orme ML, Purba HS. Pharmacokinetics of oral contraceptive steroids following the admin- 520. Silber TJ. Apparent oral contraceptive failure associated with antibiotic istration of the antimalarial drugs primaquine and chloroquine. administration. J Adolesc Health Care 1983;4:287–9.
521. Sparrow MJ. Pill method failures. N Z Med J 1987;100:102–5.
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523. Sparrow MJ. Pil method failures in women seeking abortion—fourteen 542. Karbwang J, Looareesuwan S, Back DJ, Migasana S, Bunnag D. Effect years experience. N Z Med J 1998;111:386–8.
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527. Abrams LS, Skee D, Natarajan J, Wong FA. Pharmocokinetic overview 545. Back DJ, Breckenridge AM, Crawford FE, et al. The effect of rifam- of Ortho Evra/Evra. Fertil Steril 2002;77:s3–s12.
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529. Devenport MH, Crook D, Wynn V, Lees LJ. Metabolic effects of 547. Barditch-Crovo P, Trapnell CB, Ette E, et al. The effects of rifampicin low-dose fluconazole in healthy female users and non-users of oral and rifabutin on the pharmacokinetics and pharmacodynamics of a com- contraceptives. Br J Clin Pharmacol 1989;27:851–9.
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530. Hilbert J, Messig M, Kuye O. Evaluation of interaction between flu- 548. Bolt HM, Bolt M, Kappus H. Interaction of rifampicin treatment with conazole and an oral contraceptive in healthy women. Obstet Gynecol pharmacokinetics and metabolism of ethinyloestradiol in man. Acta Endocrinol (Copenh) 1977;85:189–97.
531. Kovacs I, Somos P, Hamori M. Examination of the potential interaction 549. Gupta KC, Ali MY. Failure of oral contraceptive with rifampicin. Med between ketoconazole (Nizoral) and oral contraceptives with special J Zambia 1981;15:23.
regard to products of low hormone content (Rigevidon, anteovin). 550. Hirsch A. Sleeping pills [letter] [in French]. Nouv Presse Med Ther Hung 1986;34:167–70.
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551. Hirsch A, Til ement JP, Chretien J. Effets contrariants de la rifampicine 556. Nocke-Finke L, Breuer H, Reimers D. Effects of rifampicin on the men- sur les contraceptifs oraux: a propos de trois grossesses non desiree chez strual cycle and on oestrogen excretion in patients taking oral contra- trois malades. Rev Fr Mal Respir 1975;2:174–82.
ceptives [in German]. Deutsche Med Wochenschr 1973;98:1521–3.
552. Joshi JV, Joshi UM, Sankholi GM, et al. A study of interaction of a 557. Piguet B, Muglioni JF, Chaline G. Oral contraception and rifampicin low-dose combination oral contraceptive with anti-tubercular drugs. [letter] [in French]. Nouv Presse Med 1975;4:115–6.
558. Reimers D, Jezek A. The simultaneous use of rifampicin and other anti- 553. Kropp R. Rifampicin and oral cotnraceptives (author's transl) [in tubercular agents with oral contraceptives [in German]. Prax Pneumol German]. Prax Pneumol 1974;28:270–2.
554. LeBel M, Masson E, Guilbert E, et al. Effects of rifabutin and rifampicin 559. Skolnick JL, Stoler BS, Katz DB, Anderson WH. Rifampicin, oral on the pharmacokinetics of ethinylestradiol and norethindrone. J Clin contraceptives, and pregnancy. JAMA 1976;236:1382.
560. Szoka PR, Edgren RA. Drug interactions with oral contraceptives: 555. Meyer B, Muller F, Wessels P, Maree J. A model to detect interactions compilation and analysis of an adverse experience report database. between roxithromycin and oral contraceptives. Clin Pharmacol Ther Fertil Steril 1988;49:s31–s38.
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Appendix C
Classifications for Progestin-Only Contraceptives
Classifications for progestin-only contraceptives (POCs) not protect against sexually transmitted infections (STIs) or include those for progestin-only pills, depot medroxyproges- human immunodeficiency virus (HIV).
terone acetate, and progestin-only implants (Box). POCs do BOX. Categories for Classifying Progestin-Only Contraceptives
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for progestin-only contraceptives, including progestin-only pills, DMPA, and implants*†
Personal Characteristics and Reproductive History
Clarification: Use of POCs is not required. There is no
known harm to the woman, the course of her pregnancy, or
the fetus if POCs are inadvertently used during pregnancy.
However, the relation between DMPA use during pregnancy
and its effects on the fetus remains unclear.
a. Menarche to <18 yrs Evidence: Most studies have found that women lose
BMD while using DMPA but regain BMD after discontinu- ing DMPA. It is not known whether DMPA use among adolescents affects peak bone mass levels or whether adult women with long duration of DMPA use can regain BMD to baseline levels before entering menopause. The relation between DMPA-associated changes in BMD during the re-productive years and future fracture risk is unknown (1–41). Studies find no effect or have inconsistent results about the effects of POCs other than DMPA on BMD (42–54).
Clarification: The U.S. Department of Health and Human
a. <1 mo postpartum Services recommends that infants be exclusively breastfed b. 1 mo to <6 mos postpartum during the first 4–6 months of life, preferably for a full 6 c. ≥6 mos postpartum months. Ideally, breastfeeding should continue through the first year of life (55).
Evidence: Despite anecdotal clinical reports that POCs
might diminish milk production, direct evidence from avail-
able clinical studies demonstrates no significant negative
effect of POCs on breastfeeding performance (56–90) or on
the health of the infant (66,70,72,76–81,91–93). In general,
these studies are of poor quality, lack standard definitions of
breastfeeding or outcome measures, and have not included
premature or ill infants. Theoretical concerns about effects
of progestin exposure on the developing, neonatal brain
are based on studies of progesterone effects in animals;
whether similar effects occur after progestin exposure in
human neonates is not known.
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TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
Postpartum (in nonbreastfeeding
women)
Clarification: POCs may be started immediately
a. First trimester b. Second trimester Evidence: Limited evidence suggests that there are no
c. Immediate postseptic abortion adverse side effects when implants (Norplant) or progestin-only injectables (NET-EN) are initiated after first trimester abortion (94–97).
Past ectopic pregnancy
Comments: POP users have a higher absolute rate of
ectopic pregnancy than do users of other POCs but still less
than using no method.
History of pelvic surgery
a. Age <35 yrs i. <15 Cigarettes/day ii. ≥15 Cigarettes/day a. ≥30 kg/m2 BMI b. Menarche to <18 yrs and Evidence: Obese adolescents who used DMPA were
more likely than obese nonusers, obese COC users, and nonobese DMPA users to gain weight. These associations were not observed among adult women. One small study did not observe increases in weight gain among adolescent Norplant users by any category of baseline weight (98–105).
History of bariatric surgery§
a. Restrictive procedures: decrease Evidence: Limited evidence demonstrated no substantial
storage capacity of the stomach decrease in effectiveness of oral contraceptives among (vertical banded gastroplasty, women who underwent laparoscopic placement of an laparoscopic adjustable gastric adjustable gastric band (106).
band, laparoscopic sleeve b. Malabsorptive procedures: Evidence: Limited evidence demonstrated no substantial
decrease absorption of nutrients decrease in effectiveness of oral contraceptives among and calories by shortening the women who underwent a biliopancreatic diversion (107); functional length of the small however, evidence from pharmacokinetic studies suggested intestine (Roux-en-Y gastric bypass, biliopancreatic diversion) conflicting results of oral contraceptive effectiveness among women who underwent a jejunoileal bypass (108,109).
Comment: Bariatric surgical procedures involving a mal-
absorptive component have the potential to decrease oral
contraceptive effectiveness, perhaps further decreased by
postoperative complications, such as long-term diarrhea
and/or vomiting.
Multiple risk factors for arterial
Clarification: When multiple major risk factors exist, risk for
cardiovascular disease (such as
cardiovascular disease might increase substantially. Some older age, smoking, diabetes, and POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs. The effects of DMPA might persist for some time after discontinuation.
Hypertension
For all categories of hypertension, classifications are based on the assumption that no other risk factors exist for cardiovascular disease. When multiple risk factors do exist,
risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
a. Adequately controlled Clarification: Women adequately treated for hypertension
are at lower risk for acute myocardial infarction and stroke than are untreated women. Although no data exist, POC us-ers with adequately controlled and monitored hypertension should be at lower risk for acute myocardial infarction and stroke than are untreated hypertensive POC users.
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TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
b. Elevated blood pressure levels (properly taken measurements) i. Systolic 140–159 mm Hg or Evidence: Limited evidence suggests that among women
diastolic 90–99 mm Hg with hypertension, those who used POPs or progestin-only ii. Systolic ≥160 mm Hg or injectables had a small increased risk for cardiovascular diastolic ≥100 mm Hg§ events than did women who did not use these methods (110).
c. Vascular disease Comment: Concern exists about hypo-estrogenic effects
and reduced HDL levels, particularly among users of DMPA.
However, there is little concern about these effects with re-
gard to POPs. The effects of DMPA might persist for some
time after discontinuation
History of high blood pressure dur-
ing pregnancy (where current blood
pressure is measurable and normal)
Deep venous thrombosis (DVT)/
Pulmonary embolism (PE)
a. History of DVT/PE, not on antico- agulant therapy i. Higher risk for recurrent DVT/ PE (≥1 risk factors) • History of estrogen-associ- • Pregnancy-associated • Idiopathic DVT/PE • Known thrombophilia, including antiphospholipid • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma • History of recurrent DVT/PE ii Lower risk for recurrent DVT/ PE (no risk factors) Evidence: No direct evidence exists on use of POCs
among women with acute DVT/PE. Although findings on the
risk for venous thrombosis with use of POCs in otherwise
healthy women is inconsistent, any small increased risk is
substantially less than that with COCs (110–112).
c. DVT/PE and established on Evidence: No direct evidence exists on use of POCs
anticoagulant therapy for at least among women with DVT/PE on anticoagulant therapy. Although findings on the risk for venous thrombosis with i. Higher risk for recurrent DVT/ use of POCs are inconsistent in otherwise healthy women, PE (≥1 risk factors) any small increased risk is substantially less than that with • Known thrombophilia, including antiphospholipid Limited evidence indicates that intramuscular injections of DMPA in women on chronic anticoagulation therapy does • Active cancer (metastatic, not pose a significant risk for hematoma at the injection site on therapy, or within 6 mos or increase the risk for heavy or irregular vaginal bleeding after clinical remission), excluding non-melanoma • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/ PE (no risk factors) d. Family history (first-degree relatives) i. With prolonged immobilization ii. Without prolonged f. Minor surgery without Early Release
TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
Known thrombogenic mutations§
Clarification: Routine screening is not appropriate because
(e.g., factor V Leiden; prothrombin of the rarity of the conditions and the high cost of screening.
mutation; protein S, protein C, and antithrombin deficiencies) Superficial venous thrombosis
a. Varicose veins b. Superficial thrombophlebitis Current and history of ischemic
Initiation Continuation Initiation Continuation Comment: Concern exists about hypo-estrogenic effects
heart disease§
and reduced HDL levels, particularly among users of DMPA. However, there is little concern about these effects with re-gard to POPs. The effects of DMPA might persist for some time after discontinuation.
Stroke§ (history of cerebrovascular
Initiation Continuation Initiation Continuation Comment: Concern exists about hypo-estrogenic effects
and reduced HDL levels, particularly among users of DMPA. However, there is little concern about these effects with regard to POPs. The effects of DMPA may persist for some time after discontinuation.
Clarification: Routine screening is not appropriate because
of the rarity of the conditions and the high cost of screening.
Some types of hyperlipidemias are risk factors for vascular
disease.
Valvular heart disease
b. Complicated§ (pulmonary hyper- tension, risk for atrial fibrillation, history of subacute bacterial a. Normal or mildly impaired Evidence: No direct evidence exists on the safety of POCs
cardiac function (New York Heart among women with peripartum cardiomyopathy. Limited in- Association Functional Class I or direct evidence from noncomparative studies of women with II: patients with no limitation of ac- cardiac disease demonstrated few cases of hypertension, tivities or patients with slight, mild limitation of activity) (114) thromoboembolism, and heart failure in women with cardiac disease using POPs and DMPA (115,116).
Comment: Progestin-only implants might induce cardiac
arrhythmias in healthy women; women with peripartum car-
diomyopathy have a high incidence of cardiac arrhythmias.
b. Moderately or severely impaired Evidence: No direct evidence exists on the safety of POCs
cardiac function (New York Heart among women with peripartum cardiomyopathy. Limited in- Association Functional Class III or direct evidence from noncomparative studies of women with IV: patients with marked limitation cardiac disease demonstrated few cases of hypertension, of activity or patients who should be at complete rest) (114) thromoboembolism, and heart failure in women with cardiac disease using POPs and DMPA (115,116).
Comment: Progestin-only implants might induce cardiac
arrhythmias in healthy women; women with peripartum car-
diomyopathy have a high incidence of cardiac arrhythmias.
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TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
Systemic lupus erythematosus (SLE)§
Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in the MEC should be the same for women with
SLE who present with these conditions. For all categories of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present;
these classifications must be modified in the presence of such risk factors.
Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (117–135).
a. Positive (or unknown) antiphos- Evidence: Antiphospholipid antibodies are associated
pholipid antibodies with a higher risk for both arterial and venous thrombosis (136,137).
b. Severe thrombocytopenia Comment: Severe thrombocytopenia increases the risk for
bleeding. POCs might be useful in treating menorrhagia in
women with severe thrombocytopenia. However, given the
increased or erratic bleeding that may be seen on initiation
of DMPA and its irreversibility for 11–13 weeks after ad-
ministration, initiation of this method in women with severe
thrombocytopenia should be done with caution.
c. Immunosuppressive treatment d. None of the above a. On immunosuppressive therapy Clarification: DMPA use among women on long-term
b. Not on immunosuppressive corticosteroid therapy with a history of, or with risk factors for, nontraumatic fractures is classified as Category 3. Otherwise, DMPA use for women with rheumatoid arthritis is classified as Category 2.
Evidence: Limited evidence shows no consistent pattern of
improvement or worsening of rheumatoid arthritis with use
of oral contraceptives (138–143), progesterone (144), or
estrogen (145).
Initiation Continuation Continuation Initiation Continuation Clarification: Classification depends on accurate diagnosis
a. Non-migrainous of severe headaches that are migrainous and headaches that are not. Any new headaches or marked changes in headaches should be evaluated. Classification is for women without any other risk factors for stroke. Risk for stroke increases with age, hypertension, and smoking.
• Age <35 yrs Comment: Aura is a specific focal neurologic symptom.
• Age ≥35 yrs For more information about this and other diagnostic ii. With aura, at any age criteria, see: Headache Classification Subcommittee of the International Headache Society. The international classifica-tion of headache disorders. 2nd Ed. Cephalalgia. 2004;24 Concern exists that severe headaches might increase with use of DMPA and implants. The effects of DMPA may persist for some time after discontinuation. Clarification: If a woman is taking anticonvulsants, refer
to the section on drug interactions. Certain anticonvulsants
lower POC effectiveness.
Clarification: The classification is based on data for women
with selected depressive disorders. No data on bipolar dis-
order or postpartum depression were available. A potential
exists for drug interactions between certain antidepressant
medications and hormonal contraceptives.
Evidence: POC use did not increase depressive symp-
toms in women with depression compared with baseline
(146–149).
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TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy Comment: Irregular menstrual bleeding patterns are com-
mon among healthy women. POC use frequently induces an irregular bleeding pattern. Implant use might induce irregular bleeding patterns, especially during the first 3–6 months, but these patterns may persist longer.
b. Heavy or prolonged bleeding Clarification: Unusually heavy bleeding should raise the
(includes regular and irregular suspicion of a serious underlying condition.
Unexplained vaginal bleeding
Clarification: If pregnancy or an underlying pathological
(suspicious for serious condition) condition (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation.
Comment: POCs might cause irregular bleeding patterns,
which might mask symptoms of underlying pathology.
Before evaluation The effects of DMPA might persist for some time after discontinuation.
Benign ovarian tumors
(including cysts) Gestational trophoblastic disease
a. Decreasing or undetectable b. Persistently elevated β-hCG levels or malignant disease§ Cervical intraepithelial neoplasia
Evidence: Among women with persistent HPV infection,
long-term DMPA use (≥5 years) might increase the risk for
carcinoma in situ and invasive carcinoma (150).
Cervical cancer (awaiting treatment)
Comment: Theoretical concern exists that POC use might
affect prognosis of the existing disease. While awaiting
treatment, women may use POCs. In general, treatment of
this condition can render a woman sterile.
a. Undiagnosed mass Clarification: Evaluation should be pursued as early as
possible.
b. Benign breast disease c. Family history of cancer d. Breast cancer§ Comment: Breast cancer is a hormonally sensitive tumor,
ii. Past and no evidence of and the prognosis for women with current or recent breast current disease for 5 years cancer might worsen with POC use.
Comment: While awaiting treatment, women may use
POCs. In general, treatment of this condition renders a
woman sterile.
Comment: While awaiting treatment, women may use
POCs. In general, treatment of this condition can render a
woman sterile.
Comment: POCs do not appear to cause growth of uterine
fibroids.
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TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
Pelvic inflammatory disease (PID)
a. Past PID (assuming no current Comment: Whether POCs, like COCs, reduce the risk for
risk factors for STIs) PID among women with STIs is unknown, but they do not protect against HIV or lower genital tract STI.
i. With subsequent pregnancy ii. Without subsequent a. Current purulent cervicitis or chlamydial infection or gonorrhea b. Other STIs (excluding HIV and c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs Evidence: Evidence suggests a possible increased risk
for chlamydial cervicitis among DMPA users at high risk for
STIs. For other STIs, either evidence exists of no associa-
tion between DMPA use and STI acquisition or evidence is
too limited to draw any conclusions. No evidence is avail-
able about other POCs (151–158)
High risk for HIV
Evidence: The balance of the evidence suggests no as-
sociation between POC use and HIV acquisition, although
findings from studies of DMPA use conducted among higher
risk populations have been inconsistent (159–183).
Evidence: Most studies suggest no increased risk for HIV
disease progression with hormonal contraceptive use,
as measured by changes in CD4 cell count, viral load, or
survival. Studies observing that women with HIV who use
hormonal contraception have increased risks for STIs are
generally consistent with reports among uninfected women.
One direct study found no association between hormonal
contraceptive use and increased risk for HIV transmission to
uninfected partners; several indirect studies reported mixed
results about whether hormonal contraception is associated
with increased risk for HIV-1 DNA or RNA shedding from the
genital tract (171,184–200).
Clarification: Drug interactions might exist between
hormonal contraceptives and ARV drugs; refer to the
section on drug interactions.
Evidence: Among women with uncomplicated schistoso-
miasis, limited evidence showed that DMPA use had no
adverse effects on liver function (201).
b. Fibrosis of liver§ (if severe, see cirrhosis) Clarification: If a woman is taking rifampicin, refer to the
section on drug interactions. Rifampicin is likely to decrease the effectiveness of some POCs.
Early Release
TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
a. History of gestational disease Evidence: POCs had no adverse effects on serum lipid
levels in women with a history of gestational diabetes in 2
small studies. (202,203) Limited evidence is inconsistent
about the development of noninsulin-dependant diabetes
among users of POCs with a history of gestational diabetes
(204–207).
b. Nonvascular disease i. Noninsulin-dependent Evidence: Among women with insulin- or noninsulin-de-
ii. Insulin-dependent§ pendent diabetes, limited evidence on use of POCs (POPs, DMPA, LNG implant) suggests that these methods have little effect on short-term or long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (208–211).
c. Nephropathy/retinopathy/ Comment: Concern exists about hypo-estrogenic effects
and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
d. Other vascular disease or Comment: Concern exists about hypo-estrogenic effects
diabetes of >20 yrs' duration§ and reduced HDL levels, particularly among users of DMPA. The effects of DMPA might persist for some time after discontinuation. Some POCs might increase the risk for thrombosis, although this increase is substantially less than with COCs.
Inflammatory bowel disease (IBD)
Evidence: Risk for disease relapse among women with
(ulcerative colitis, Crohn disease) IBD using oral contraceptives (most studies did not specify formulation) did not increase significantly from that for nonusers (212–216).
Comment: Absorption of POPs among women with IBD
might be reduced if the woman has substantial malabsorp-
tion caused by severe disease or small bowel surgery.
Women with IBD have a higher prevalence than the general population of osteoporosis and osteopenia. Use of DMPA, which has been associated with small changes in BMD, might be of concern.
i. Treated by cholecystectomy ii. Medically treated History of cholestasis
a. Pregnancy-related b. Past COC–related Comment: Theoretically, a history of COC-related cholesta-
sis might predict subsequent cholestasis with POC use.
However, this has not been documented.
a. Acute or flare Early Release
May 28, 2010
TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
a. Mild (compensated) b. Severe§ (decompensated) Liver tumors
Evidence: Limited direct evidence suggests that hormonal
i. Focal nodular hyperplasia contraceptive use does not influence either progression or regression of liver lesions among women with focal nodular ii. Hepatocellular adenoma§ b. Malignant§ (hepatoma) Comment: No evidence is available about hormonal con-
traceptive use among women with hepatocellular adenoma.
COC use in healthy women is associated with development
and growth of hepatocellular adenoma; whether other hor-
monal contraceptives have similar effects is not known.
Sickle cell disease§
Evidence: Among women with sickle cell disease, POC use
did not have adverse effects on hematologic parameters
and, in some studies, was beneficial with respect to clinical
symptoms (219–226).
Iron deficiency anemia
Comment: Changes in the menstrual pattern associated
with POC use have little effect on hemoglobin levels.
Solid Organ Transplantation
Solid organ transplantaton§
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy Antiretroviral (ARV) therapy
Clarification: ARV drugs have the potential to either
a. Nucleoside reverse transcriptase decrease or increase the bioavailability of steroid hormones inhibitors (NRTIs) in hormonal contraceptives. Limited data (Appendix M) sug- b. Non-nucleoside reverse tran- gest potential drug interactions between many ARV drugs scriptase inhibitors (NNRTIs) (particularly some NNRTIs and ritonavir-boosted protease c. Ritonavir-boosted protease inhibitors) and hormonal contraceptives. These interactions may alter the safety and effectiveness of both the hormonal contraceptive and the ARV drug. Thus, if a woman on ARV treatment decides to initiate or continue hormonal contra-ceptive use, the consistent use of condoms is recommend-ed to both prevent HIV transmission and compensate for any possible reduction in the effectiveness of the hormonal contraceptive.
a. Certain anticonvulsants (pheny- Clarification: Although the interaction of certain anticon-
toin, carbamazepine, barbitu- vulsants with POPs and ETG implants is not harmful to rates, primidone, topiramate, women, it is likely to reduce the effectiveness of POPs and ETG implants. Whether increasing the hormone dose of POPs alleviates this concern remains unclear. Use of other contraceptives should be encouraged for women who are long-term users of any of these drugs. Use of DMPA is a Category 1 because its effectiveness is not decreased by use of certain anticonvulsants.
Evidence: Use of certain anticonvulsants may decrease the
effectiveness of POCs (227–229)
Evidence: No drug interactions have been reported among
epileptic women taking lamotrigine and using POCs (230)
Early Release
TABLE. (Continued) Classifications for progestin-only contraceptives,*† including progestin-only pills, DMPA, and implants
a. Broad-spectrum antibiotics c. Antiparasitics d. Rifampicin or rifabutin therapy Clarification: Although the interaction of rifampicin or rifab-
utin with POPs and ETG implants is not harmful to women,
it is likely to reduce the effectiveness of POPs and ETG
implants. Use of other contraceptives should be encouraged
for women who are long-term users of any of these drugs.
Use of DMPA is a Category 1 because its effectiveness is
not decreased by use of rifampicin or rifabutin. Whether in-
creasing the hormone dose of POPs alleviates this concern
remains unclear.
* Abbreviations: STI = sexually transmitted infection; HIV = human immunodeficiency virus; POC = progestin-only contraceptive; DMPA = depot medroxyprogesterone acetate; BMD = bone mineral density; NET-EN = norethisterone enantate; BMI = body mass index; COC = combined oral contraceptive; HDL = high-density lipoprotein; POP = progestin- only pill; DVT = deep venous thrombosis; PE = pulmonary embolism; SLE = systemic lupus erythematosus; VTE = venous thromboembolism; MEC = Medical Eligibility Criteria; hCG = human chorionic gonadotropin; HPV = human papillomavirus; PID = pelvic inflammatory disease; AIDS = acquired immunodeficiency syndrome; IBD = inflammatory bowel disease; ARV = antiretroviral; LNG = levonorgestrel; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; ETG = † POCs do not protect against STI/HIV. If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission.
§ Condition that exposes a woman to increased risk as a result of unintended pregnancy.
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Appendix D
Classifications for Emergency Contraceptive Pills
Classifications for emergency contraceptive pills (ECPs) are ECPs do not protect against sexually transmitted infections for both levonorgestrel and combined oral contraceptive pills. (STIs) or human immunodeficiency virus (HIV).
BOX. Categories for Classifying Emergency Contraceptive Pills
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for emergency contraceptive pills, including levonorgestrel contraceptive pills and combined oral
contraceptive pills*†
Personal Characteristics and Reproductive History
Clarification: Although this method is not indicated for a woman with a known or
suspected pregnancy, no harm to the woman, the course of her pregnancy, or the fetus if ECPs are inadvertently used is known to exist. Past ectopic pregnancy
History of bariatric surgery§
a. Restrictive procedures: decrease storage capacity of the stom- ach (vertical banded gastroplasty, laparoscopic adjustable gastric band, laparoscopic sleeve gastrectomy) b. Malabsorptive procedures: decrease absorption of nutrients Comment: Bariatric surgical procedures involving a malabsorptive component
and calories by shortening the functional length of the small have the potential to decrease oral contraceptive effectiveness, perhaps further intestine (Roux-en-Y gastric bypass, biliopancreatic diversion) decreased by postoperative complications such as long-term diarrhea and/or vomiting. Because of these malabsorptive concerns, an emergency IUD might be more appropriate than ECPs.
History of severe cardiovascular complications§ (ischemic
Comment: The duration of ECP use is less than that of regular use of COCs or
heart disease, cerebrovascular attack, or other thromboembolic POPs and thus would be expected to have less clinical impact.
Comment: The duration of ECP use is less than that of regular use of COCs or
POPs and thus would be expected to have less clinical impact.
a. On immunosuppressive therapy b. Not on immunosuppressive therapy Comment: The duration of ECP use is less than that of regular use of COCs or
POPs and thus would be expected to have less clinical impact.
Inflammatory bowel disease (ulcerative colitis, Crohn disease)
Severe liver disease§ (including jaundice)
Comment: The duration of ECP use is less than that of regular use of COCs or
POPs and thus would be expected to have less clinical impact.
Solid Organ Transplantation
Solid organ transplantation§
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy Early Release
TABLE. (Continued) Classifications for emergency contraceptive pills, including levonorgestrel contraceptive pills and combined
oral contraceptive pills*†
Repeated ECP use
Clarification: Recurrent ECP use is an indication that the woman requires further
counseling about other contraceptive options. Frequently repeated ECP use may be harmful for women with conditions classified as 2, 3, or 4 for CHC or POC use. Comment: Use of ECPs in cases of rape has no restrictions.
* Abbreviations: STI = sexually transmitted infection; HIV = human immunodeficiency virus; ECP, emergency contraceptive pill; IUD = intrauterine device; COC = combined oral contraceptive; POP = progestin-only pill; CHC = combined hormonal contraceptive; POC = progestin-only contraceptive † ECPs do not protect against STI/HIV. If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission.
§ Condition that exposes a woman to increased risk as a result of unintended pregnancy.
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Appendix E
Classifications for Intrauterine Devices
Classifications for intrauterine devices (IUDs) are for the transmitted infections (STIs) or human immunodeficiency levonorgestrel-releasing (20 μg/24 hours) IUD and the copper- virus (HIV).
bearing IUD (Box). IUDs do not protect against sexual y BOX. Categories for Classifying Intrauterine Devices
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for intrauterine devices, including the LNG-IUD and the Cu-IUD*†
Personal Characteristics and Reproductive History
Clarification: The IUD is not indicated during pregnancy and
should not be used because of the risk for serious pelvic infection and septic spontaneous abortion.
a. Menarche to <20 yrs Comment: Concern exists about both the risk for expulsion from
nulliparity and for STIs from sexual behaviour in younger age Evidence: Data conflict about whether IUD use is associated
with infertility among nulliparous women, although well-conducted studies suggest no increased risk (1–9).
Postpartum (breastfeeding or nonbreast-
feeding women, including post-Cesarean a. <10 minutes after delivery of the Evidence: Immediate postpartum Cu-IUD insertion, particularly
when insertion occurs immediately after delivery of the placenta, is b. 10 minutes after delivery of the associated with lower expulsion rates than is delayed postpartum placenta to <4 wks insertion up to 72 hours postpartum; no data exist that examine times >72 hours postpartum. In addition, postplacental placement at the time of Cesarean section has lower expulsion rates than does postplacental vaginal insertions. Insertion complications of perforation and infection are not increased by Cu-IUD placement at any time during the postpartum period (10–23). No evidence is available that compares different insertion times for the LNG-IUD.
d. Puerperal sepsis Comment: Insertion of an IUD might substantially worsen the
a. First trimester Clarification: IUDs can be inserted immediately after first trimes-
b. Second trimester ter spontaneous or induced abortion.
Evidence: Risk for complications from immediate versus delayed
insertion of an IUD after abortion did not differ. Expulsion was greater when an IUD was inserted after a second trimester abor- tion than when inserted after a first trimester abortion. Safety or expulsion for postabortion insertion of an LNG-IUD did not differ from that of a Cu-IUD (24–37).
c. Immediate postseptic abortion Comment: Insertion of an IUD might substantially worsen the
Early Release
TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
Past ectopic pregnancy
Comment: The absolute risk for ectopic pregnancy is extremely
low because of the high effectiveness of IUDs. However, when a woman becomes pregnant during IUD use, the relative likelihood of ectopic pregnancy increases greatly.
History of pelvic surgery (see Postpartum,
including post-Cesarean section) a. Age <35 yrs i. <15 Cigarettes/day ii. ≥15 Cigarettes/day Obesity
a. ≥30 kg/m2 BMI
b. Menarche to <18 yrs and ≥30 kg/m2 BMI History of bariatric surgery§
a. Restrictive procedures: decrease stor- age capacity of the stomach (vertical banded gastroplasty, laparoscopic adjustable gastric band, laparoscopic sleeve gastrectomy) b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small intestine (Roux-en-Y gastric bypass, biliopancreatic diversion) Multiple risk factors for arterial cardio-
vascular disease (such as older age,
smoking, diabetes, and hypertension) Hypertension
For all categories of hypertension, classifications are based on the assumption that no other risk factors for cardiovascular disease exist. When multiple risk factors do exist,
risk for cardiovascular disease might increase substantially. A single reading of blood pressure level is not sufficient to classify a woman as hypertensive.
a. Adequately controlled hypertension b. Elevated blood pressure levels (properly taken measurements) i. Systolic 140–159 mm Hg or diastolic ii. Systolic ≥160 mm Hg or diastolic Comment: Theoretical concern exists about the effect of LNG on
lipids. Use of Cu-IUDs has no restrictions.
c. Vascular disease Comment: Theoretical concern exists about the effect of LNG on
lipids. Use of Cu-IUDs has no restrictions.
History of high blood pressure during
pregnancy (where current blood pressure is
measurable and normal) Deep venous thrombosis (DVT)/
pulmonary embolism (PE)
a. History of DVT/PE, not on anticoagulant therapy i. Higher risk for recurrent DVT/PE (≥1 • History of estrogen-associated • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non- melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no Early Release
May 28, 2010
TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
Evidence: No direct evidence exists on the use of POCs among
women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (38–40).
c. DVT/PE and established on anticoagu- Evidence: No direct evidence exists on the use of POCs among
lant therapy for at least 3 mos women with acute DVT/PE. Although findings on the risk for venous thrombosis with the use of POCs in otherwise healthy women are inconsistent, any small increased risk is substantially less than that with COCs (38–40).
Evidence: Limited evidence indicates that insertion of the LNG-
IUD does not pose major bleeding risks in women on chronic anticoagulant therapy. (41–44)
Comment: The LNG-IUD might be a useful treatment for menor-
rhagia in women on long-term chronic anticoagulation therapy.
i. Higher risk for recurrent DVT/PE (≥1 • Known thrombophilia, including • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non- melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no d. Family history (first-degree relatives) i. With prolonged immobilization ii. Without prolonged immobilization f. Minor surgery without immobilization Known thrombogenic mutations§ (e.g.,
Clarification: Routine screening is not appropriate because of the
factor V Leiden; prothrombin mutation; rarity of the conditions and the high cost of screening.
protein S, protein C, and antithrombin Superficial venous thrombosis
a. Varicose veins b. Superficial thrombophlebitis Current and history of ischemic heart
Comment: Theoretical concern exists about the effect of LNG on
lipids. Use of Cu-IUDs has no restrictions.
Stroke§ (history of cerebrovascular
Comment: Theoretical concern exists about the effect of LNG on
lipids. Use of Cu-IUDs has no restrictions.
Clarification: Routine screening is not appropriate because of the
rarity of the condition and the high cost of screening. Valvular heart disease
Comment: According to the American Heart Association, admin-
istration of prophylactic antibiotics solely to prevent endocarditis is not recommended for patients who undergo genitourinary tract procedures, including insertion or removal of IUDs (45).
b. Complicated§ (pulmonary hyperten- Comment: According to the American Heart Association, admin-
sion, risk for atrial fibrillation, history of istration of prophylactic antibiotics solely to prevent endocarditis subacute bacterial endocarditis) is not recommended for patients who undergo genitourinary tract procedures, including insertion or removal of IUDs (45).
a. Normal or mildly impaired cardiac Evidence: No direct evidence exists on the safety of IUDs among
function (New York Heart Association women with peripartum cardiomyopathy. Limited indirect evidence Functional Class I or II: patients with no from noncomparative studies did not demonstrate any cases of limitation of activities or patients with arrhythmia or infective endocarditis in women with cardiac disease slight, mild limitation of activity) (46) who used IUDs (47,48).
Comment: IUD insertion might induce cardiac arrhythmias in
healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
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TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
b. Moderately or severely impaired cardiac Evidence: There is no direct evidence on the safety of IUDs
function (New York Heart Association among women with peripartum cardiomyopathy. Limited indirect Functional Class III or IV: patients with evidence from noncomparative studies did not demonstrate any marked limitation of activity or patients cases of arrhythmia or infective endocarditis in women with car- who should be at complete rest) (46) diac disease who used IUDs (47,48).
Comment: IUD insertion might induce cardiac arrhythmias in
healthy women; women with peripartum cardiomyopathy have a high incidence of cardiac arrhythmias.
Systemic lupus erythematosus (SLE)§
Persons with SLE are at increased risk for ischemic heart disease, stroke, and VTE. Categories assigned to such conditions in the MEC should be the same for women
with SLE who have these conditions. For all categories of SLE, classifications are based on the assumption that no other risk factors for cardiovascular disease are present; these classifications must be modified in the presence of such risk factors.
Many women with SLE can be considered good candidates for most contraceptive methods, including hormonal contraceptives (43,49–66).
a. Positive (or unknown) antiphospholipid Evidence: Antiphospholipid antibodies are associated with a
higher risk for both arterial and venous thrombosis (67,68).
b. Severe thrombocytopenia Clarification: Severe thrombocytopenia increases the risk for
bleeding. The category should be assessed according to the severity of thrombocytopenia and its clinical manifestations. In women with very severe thrombocytopenia who are at risk for spontaneous bleeding, consultation with a specialist and certain pretreatments might be warranted.
Evidence: The LNG-IUD might be a useful treatment for menor-
rhagia in women with severe thrombocytopenia (43).
c. Immunosuppressive treatment d. None of the above a. On immunosuppressive therapy b. Not on immunosuppressive therapy Clarification: Any new headaches or marked changes in head-
aches should be evaluated.
a. Non-migrainous (mild or severe) Comment: Aura is a specific focal neurologic symptom. For more
• Age <35 yrs information about this and other diagnostic criteria, see: Headache Classification Subcommittee of the International Headache • Age ≥35 yrs Society. The international classification of headache disorders. ii. With aura, at any age 2nd ed. Cephalalgia 2004;24(Suppl 1):1– 150. Available from .
Clarification: The classification is based on data for women with
selected depressive disorders. No data were available on bipolar disorder or postpartum depression. Drug interactions potentially can occur between certain antidepressant medications and hor- Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
a. Irregular pattern without heavy bleeding b. Heavy or prolonged bleeding (includes Clarification: Unusually heavy bleeding should raise suspicion of
regular and irregular patterns) a serious underlying condition.
Evidence: Evidence from studies examining the treatment effects
of the LNG-IUD among women with heavy or prolonged bleeding reported no increase in adverse effects and found the LNG-IUD to be beneficial in treating menorrhagia (69–76).
Unexplained vaginal bleeding (suspicion
Clarification: If pregnancy or an underlying pathological condition
for serious condition) Continuation (such as pelvic malignancy) is suspected, it must be evaluated and the category adjusted after evaluation. The IUD does not Before evaluation need to be removed before evaluation.
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TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
Evidence: LNG-IUD use among women with endometriosis de-
creased dysmenorrhea, pelvic pain, and dyspareunia (77–81).
Benign ovarian tumors (including cysts)
Comment: Dysmenorrhea might intensify with Cu-IUD use. LNG-
IUD use has been associated with reduction of dysmenorrhea.
Gestational trophoblastic disease
a. Decreasing or undetectable β–hCG Evidence: Limited evidence suggests that women using an IUD
after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (82–84).
b. Persistently elevated β-hCG levels or Evidence: Limited evidence suggests that women using an IUD
malignant disease§ after uterine evacuation for a molar pregnancy are not at greater risk for postmolar trophoblastic disease than are women using other methods of contraception (82–84) Cervical intraepithelial neoplasia
Comment: Theoretical concern exists that LNG-IUDs might
enhance progression of cervical intraepithelial neoplasia.
Cervical cancer (awaiting treatment)
Continuation Comment: Concern exists about the increased risk for infection
and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment, but until then, the woman is at risk for pregnancy.
a. Undiagnosed mass b. Benign breast disease c. Family history of cancer d. Breast cancer§ Comment: Breast cancer is a hormonally sensitive tumor.
Concerns about progression of the disease might be less with LNG-IUDs than with COCs or higher-dose POCs.
ii. Past and no evidence of current disease for 5 yrs Evidence: Among women with endometrial hyperplasia, no
adverse health events occurred with LNG-IUD use; most women experienced disease regression (85–93).
Continuation Comment: Concern exists about the increased risk for infection,
perforation, and bleeding at insertion. The IUD most likely will need to be removed at the time of treatment, but until then, the woman is at risk for pregnancy.
Comment: Women with ovarian cancer who undergo fertility spar-
ing treatment and need contraception may use an IUD.
Evidence: Among women with uterine fibroids using an LNG-IUD,
most experienced improvements in serum levels of hemoglobin, hematocrit, and ferritin (73,94–100) and menstrual blood loss (73,75,94–101). Rates of LNG-IUD expulsion were higher in women with uterine fibroids (11%) than in women without fibroids (0%–3%); these findings were not statistically significant or sig- nificance testing was not conducted (75,101). Rates of expulsion from noncomparative studies ranged from 0%–20% (94,96–100).
Comment: Women with heavy or prolonged bleeding should be
assigned the category for that condition.
a. Distorted uterine cavity (any congenital Comment: An anatomic abnormality that distorts the uterine cav-
or acquired uterine abnormality distort- ity might preclude proper IUD placement.
ing the uterine cavity in a manner that is incompatible with IUD insertion) b. Other abnormalities (including cervical stenosis or cervical lacerations) not distorting the uterine cavity or interfering with IUD insertion Early Release
TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
Pelvic inflammatory disease (PID)
a. Past PID (assuming no known current Comment: IUDs do not protect against STI/HIV/PID. In women
risk factors for STIs) at low risk for STIs, IUD insertion poses little risk for PID. Current risk for STIs and desire for future pregnancy are relevant i. With subsequent pregnancy ii. Without subsequent pregnancy Clarification for continuation: Treat the PID using appropri-
ate antibiotics. The IUD usually does not need to be removed if the woman wishes to continue using it. Continued use of an IUD depends on the woman's informed choice and her current risk factors for STIs and PID.
Evidence: Among IUD users treated for PID, clinical course did
not differ regardless of whether the IUD was removed or left in a. Current purulent cervicitis or chlamydial Clarification for continuation: Treat the STI using appropri-
infection or gonorrhea ate antibiotics. The IUD usually does not need to be removed if the woman wishes to continue using it. Continued use of an IUD depends on the woman's informed choice and her current risk factors for STIs and PID.
Evidence: No evidence exists about whether IUD insertion among
women with STIs increases the risk for PID over that of women with no IUD insertion. Among women who had an IUD inserted, the absolute risk for subsequent PID was low among women with STI at the time of insertion but greater than among women with no STI at the time of IUD insertion (105–111).
b. Other STIs (excluding HIV and hepatitis) c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs Clarification for initiation: If a woman has a very high individual
likelihood of exposure to gonorrhea or chlamydial infection, the condition is a Category 3.
Evidence: Using an algorithm to classify STI risk status among
IUD users, 1 study reported that 11% of women at high risk for STIs experienced IUD-related complications compared with 5% of those not classified as high risk (107).
High risk for HIV
Evidence: Among women at risk for HIV, Cu-IUD use did not
increase risk for HIV acquisition (112–122).
Evidence: Among IUD users, limited evidence shows no higher
risk for overall complications or for infectious complications in HIV- infected than in HIV-uninfected women. IUD use did not adversely affect progression of HIV when compared with hormonal contra- ceptive use among HIV-infected women. Furthermore, IUD use among HIV-infected women was not associated with increased risk for transmission to sex partners (112,123–130).
Clarification for continuation: IUD users with AIDS should be
closely monitored for pelvic infection.
Clinically well on ARV therapy b. Fibrosis of the liver§ (if severe, see Comment: Insertion of an IUD may substantially worsen the
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TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
a. History of gestational disease b. Nonvascular disease Evidence: Limited evidence on the use of the LNG-IUD among
i. Noninsulin-dependent women with insulin-dependent or noninsulin-dependent diabetes suggests that these methods have little effect on short-term or ii. Insulin-dependent§ long-term diabetes control (e.g., glycosylated hemoglobin levels), hemostatic markers, or lipid profile (131,132).
d. Other vascular disease or diabetes of >20 yrs' duration§ Inflammatory bowel disease (IBD)
Evidence: Although two case reports described three women with
(ulcerative colitis, Crohn disease) IBD who experienced exacerbation of disease 5 days–25 months after LNG-IUD insertion (133,134), no comparative studies have examined the safety of IUD use among women with IBD.
i. Treated by cholecystectomy ii. Medically treated History of cholestasis
a. Pregnancy-related b. Past COC-related Comment: Concern exists that history of COC-related cholestasis
might predict subsequent cholestasis with LNG use. Whether risk exists with use of LNG-IUD is unclear.
a. Acute or flare a. Mild (compensated) b. Severe§ (decompensated) Liver tumors
i. Focal nodular hyperplasia ii. Hepatocellular adenoma§ Comment: No evidence is available about hormonal contracep-
tive use in women with hepatocellular adenoma. COC use in healthy women is associated with development and growth of hepatocellular adenoma; whether other hormonal contraceptives have similar effects is not known.
b. Malignant§ (hepatoma) Comment: Concern exists about an increased risk for blood loss
with Cu-IUDs.
Sickle cell disease§
Comment: Concern exists about an increased risk for blood loss
with Cu-IUDs.
Iron deficiency anemia
Comment: Concern exists about an increased risk for blood loss
with Cu-IUDs.
Solid Organ Transplantation
Solid organ transplantation§
Continuation Evidence: No comparative studies have examined IUD use
a. Complicated: graft failure (acute or among transplant patients. Four case reports of transplant chronic), rejection, cardiac allograft patients using IUDs provided inconsistent results, including ben- eficial effects and contraceptive failures (135–138).
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TABLE. (Continued) Classifications for intrauterine devices,*† including the LNG-IUD and the Cu-IUD
Antiretroviral (ARV) therapy
Continuation Clarification: No known interaction exists between ARV therapy
a. Nucleoside reverse transcriptase inhibi- and IUD use. However, AIDS as a condition is classified as Category 3 for insertion and Category 2 for continuation unless the woman is clinically well on ARV therapy, in which case, both b. Non-nucleoside reverse transcriptase insertion and continuation are classified as Category 2 (see AIDS inhibitors (NNRTIs) c. Ritonavir-boosted protease inhibitors a. Certain anticonvulsants (phenytoin, Evidence: Limited evidence suggests use of certain anticonvul-
carbamazepine, barbiturates, primidone, sants does not interfere with the contraceptive effectiveness of the Evidence: No drug interactions have been reported among epi-
leptic women taking lamotrigine and using the LNG-IUD (140).
a. Broad-spectrum antibiotics c. Antiparasitics d. Rifampicin or rifabutin therapy Evidence: One cross-sectional survey found that rifabutin had no
impact on the effectiveness of the LNG-IUD (139).
* Abbreviations: LNG-IUD = levonorgestrel-releasing intrauterine device; Cu-IUD = copper IUD; STI = sexually transmitted infection; HIV = human immunodeficiency virus; BMI = body mass index; DVT = deep venous thrombosis; PE = pulmonary embolism; POC = progestin-only contraceptive; COC = combined oral contraceptive; SLE = systemic lupus erythematosus; MEC = Medical Eligibility Criteria; hCG = human chorionic gonadotropin; PID = pelvic inflammatory disease; AIDS = acquired immunodeficiency syndrome; ARV = antiretroviral; IBD = inflammatory bowel disease; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor.
† IUDs do not protect against STI/HIV. If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission § Condition that exposes a woman to increased risk as a result of unintended pregnancy.
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68. Wahl DG, Guillemin F, de Maistre E, et al. Risk for venous thrombosis releasing intrauterine system (LNG-IUS) in the treatment of endome- related to antiphospholipid antibodies in systemic lupus erythematosus— trial hyperplasia—a long-term follow-up study. Eur J Obstet Gynecol a meta-analysis. Lupus 1997;6:467–73.
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Appendix F
Classifications for Copper Intrauterine Devices for
A copper IUD (Cu-IUD) can be used within 5 days of The eligibility criteria for interval Cu-IUD insertion also unprotected intercourse as an emergency contraceptive. apply for the insertion of Cu-IUDs as emergency contracep- However, when the time of ovulation can be estimated, the tion (Box). Cu-IUDs for emergency contraception do not Cu-IUD can be inserted beyond 5 days after intercourse, if protect against sexual y transmitted infections (STIs) or human necessary, as long as the insertion does not occur >5 days after immunodeficiency virus (HIV).
BOX. Categories for Classifying Cu-IUDs as Emergency Contraception
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for copper intrauterine devices for emergency contraception*†
Condition
Clarification: IUD use is not indicated during pregnancy and should not be used because
of the risk for serious pelvic infection and septic spontaneous abortion.
a. High risk for STI Comment: IUDs do not protect against STI/HIV or PID. Among women with chlamydial
infection or gonorrhea, the potential increased risk for PID with IUD insertion should be avoided. The concern is less for other STIs.
b. Low risk for STI * Abbreviations: IUD = intrauterine device; Cu-IUD = copper IUD; STI = sexually transmitted infection; HIV = human immunodeficiency virus; PID = pelvic inflammatory disease † Cu-IUDs for emergency contraception do not protect against STI/HIV. If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission.
Early Release
Appendix G
Classifications for Barrier Methods
Classifications for barrier contraceptive methods include Women with conditions that make pregnancy an unaccept- those for condoms, which include male latex condoms, male able risk should be advised that barrier methods for pregnancy polyurethane condoms, and female condoms; spermicides; and prevention may not be appropriate for those who cannot use diaphragm with spermicide or cervical cap (Box). Consistent them consistently and correctly because of the relatively higher and correct use of the male latex condom reduces the risk for typical-use failure rates of these methods.
BOX. Categories for Classifying Barrier Methods
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
Personal Characteristics and Reproductive History
Clarification: None of these methods are relevant for contraception during known
applicable pregnancy. However, for women who remain at risk for STI/HIV during pregnancy, the correct and consistent use of condoms is recommended.
a. Menarche to <40 yrs Clarification: Risk for cervical cap failure is higher in parous women than in
nulliparous women.
a. <6 wks postpartum Clarification: Diaphragm and cap are unsuitable until uterine involution is
b. ≥6 wks postpartum a. First trimester b. Second trimester Clarification: Diaphragm and cap are unsuitable until 6 weeks after second
trimester abortion.
c. Immediate postseptic abortion Past ectopic pregnancy
History of pelvic surgery
a. Age <35 yrs i. <15 Cigarettes/day ii. ≥15 Cigarettes/day Comment: Severe obesity might make diaphragm and cap placement difficult.
a. ≥30 kg/m2 BMI b. Menarche to <18 yrs and ≥30 kg/m2 BMI History of bariatric surgery§
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gas- troplasty, laparoscopic adjustable gastric band, laparoscopic sleeve gastrectomy) Early Release
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TABLE. (Continued) Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
b. Malabsorptive procedures: decrease absorp- tion of nutrients and calories by shortening the functional length of the small intestine (Roux- en-Y gastric bypass, biliopancreatic diversion) Multiple risk factors for arterial cardiovascular
disease (such as older age, smoking, diabetes,
and hypertension) a. Adequately controlled hypertension b. Elevated blood pressure levels (properly taken measurements) i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg ii. Systolic ≥160 mm Hg or diastolic ≥100 mm c. Vascular disease History of high blood pressure during
pregnancy (where current blood pressure is
measurable and normal) Deep venous thrombosis (DVT)/pulmonary
a. History of DVT/PE, not on anticoagulant therapy i. Higher risk for recurrent DVT/PE (≥1 risk • History of estrogen-associated DVT/PE • Pregnancy-associated DVT/PE • Idiopathic DVT/PE • Known thrombophilia, including antiphos- pholipid syndrome • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no risk c. DVT/PE and established on anticoagulant therapy for at least 3 mos i. Higher risk for recurrent DVT/PE (≥1 risk • Known thrombophilia, including antiphos- pholipid syndrome • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no risk d. Family history (first-degree relatives) i. With prolonged immobilization ii. Without prolonged immobilization f. Minor surgery without immobilization Known thrombogenic mutations§ (e.g., factor V
Clarification: Routine screening is not appropriate because of the rarity of the
Leiden; prothrombin mutation; protein S, protein C, conditions and the high cost of screening.
and antithrombin deficiencies) Early Release
TABLE. (Continued) Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
Superficial venous thrombosis
a. Varicose veins b. Superficial thrombophlebitis Current and history of ischemic heart disease§
Stroke§ (history of cerebrovascular accident)
Clarification: Routine screening is not appropriate because of the rarity of the
conditions and the high cost of screening.
Valvular heart disease
b. Complicated§ (pulmonary hypertension, risk for atrial fibrillation, history of subacute bacterial a. Normal or mildly impaired cardiac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (1) i. <6 mos b. Moderately or severely impaired cardiac func- tion (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at com- plete rest) (1) Systemic lupus erythematosus§
a. Positive (or unknown) antiphospholipid b. Severe thrombocytopenia c. Immunosuppressive treatment d. None of the above a. On immunosuppressive therapy b. Not on immunosuppressive therapy a. Non-migrainous (mild or severe) • Age <35 yrs • Age ≥35 yrs ii. With aura, at any age Reproductive Tract Infections and Disorders
Unexplained vaginal bleeding
(suspicious for serious condition) Before evaluation Clarification: If pregnancy or an underlying pathological condition (such as pelvic
malignancy) is suspected, it must be evaluated and the category adjusted after Benign ovarian tumors (including cysts)
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TABLE. (Continued) Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
Gestational trophoblastic disease
a. Decreasing or undetectable β–hCG levels b. Persistently elevated β-hCG levels or malignant disease§ Cervical intraepithelial neoplasia
Clarification: The cap should not be used. Diaphragm use has no restrictions.
Cervical cancer (awaiting treatment)
Clarification: The cap should not be used. Diaphragm use has no restrictions.
Comment: Repeated and high-dose use of nonoxynol-9 can cause vaginal and
cervical irritation or abrasions.
a. Undiagnosed mass b. Benign breast disease c. Family history of cancer d. Breast cancer§ ii. Past and no evidence of current disease Clarification: The diaphragm cannot be used in certain cases of prolapse. Cap
applicable use is not appropriate for a woman with markedly distorted cervical anatomy.
Pelvic inflammatory disease (PID)
a. Past PID (assuming no current risk factors of STIs) i. With subsequent pregnancy ii. Without subsequent pregnancy a. Current purulent cervicitis or chlamydial infec- tion or gonorrhea b. Other STIs (excluding HIV and hepatitis) c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs HIV/AIDS
High risk for HIV
Evidence: Repeated and high-dose use of the spermicide nonoxynol-9 was as-
sociated with increased risk for genital lesions, which might increase the risk for HIV infection (2).
Comment: Diaphragm use is assigned Category 4 because of concerns about
the spermicide, not the diaphragm.
Comment: Use of spermicides and/or diaphragms (with spermicide) can disrupt
the cervical mucosa, which may increase viral shedding and HIV transmission to uninfected sex partners.
Comment: Use of spermicides and/or diaphragms (with spermicide) can disrupt
the cervical mucosa, which may increase viral shedding and HIV transmission to uninfected sex partners b. Fibrosis of liver§ Early Release
TABLE. (Continued) Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
History of toxic shock syndrome
Comment: Toxic shock syndrome has been reported in association with contra-
ceptive sponge and diaphragm use.
Urinary tract infection
Comment: Use of diaphragms and spermicides might increase risk for urinary
tract infection.
a. History of gestational disease b. Nonvascular disease i. Noninsulin-dependent ii. Insulin-dependent§ d. Other vascular disease or diabetes of >20 yrs' Inflammatory bowel disease
(ulcerative colitis, Crohn disease) i. Treated by cholecystectomy ii. Medically treated History of cholestasis
a. Pregnancy-related b. Past COC-related a. Acute or flare a. Mild (compensated) b. Severe§ (decompensated) Liver tumors
i. Focal nodular hyperplasia ii. Hepatocellular adenoma§ b. Malignant§ (hepatoma) Sickle cell disease§
Iron deficiency anemia
Solid Organ Transplantation
Solid organ transplantation§
a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft vasculopathy Early Release
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TABLE. (Continued) Classifications for barrier methods,*† including condoms, spermicides, and diaphragms/caps
Antiretroviral (ARV) therapy
Clarification: No drug interaction between ARV therapy and barrier method
use is known. However, HIV infection and AIDS are classified as Category 3 for spermicides and diaphragms (see HIV/AIDS condition above).
a. Nucleoside reverse transcriptase inhibitors b. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) c. Ritonavir-boosted protease inhibitors a. Certain anticonvulsants (phenytoin, carbam- azepine, barbiturates, primidone, topiramate, a. Broad-spectrum antibiotics c. Antiparasitics d. Rifampicin or rifabutin Allergy to latex
Clarification: The condition of allergy to latex does not apply to plastic condoms/
* Abbreviations: STI = sexually transmitted infection; HIV = human immunodeficiency virus; BMI, body mass index; DVT = deep venous thrombosis; PE = pulmonary embolism; ARV = antiretroviral; hCG = human chorionic gonadotropin; PID = pelvic inflammatory disease; AIDS = acquired immunodeficiency syndrome; COC = combined oral contracep- tive; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor.
† If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission. Women with conditions that make pregnancy an unacceptable risk should be advised that barrier methods for pregnancy prevention may not be appropriate for those who cannot use them consistently and correctly because of the relatively higher typical-use failure rates of these methods.
§ Condition that exposes a woman to increased risk as a result of unintended pregnancy.
1. The Criteria Committee of the New York Heart Association. Nomenclature 2. Wilkinson D, Ramjee G, Tholandi M, Rutherford G. Nonoxynol-9 for and criteria for diagnosis of diseses of the heart and great vessels. 9th ed. preventing vaginal acquisition of HIV infection by women from men. Boston, MA: Little, Brown & Co; 1994. Cochrane Database Syst Rev 2002;4:CD003939.
Early Release
Appendix H
Classifications for Fertility Awareness–Based Methods
Fertility awareness–based (FAB) methods of family planning Box. Definitions for terms associated with fertility awareness–
involve identifying the fertile days of the menstrual cycle, whether by observing fertility signs such as cervical secretions and basal body temperature or by monitoring cycle days (Box). • Symptoms-based methods: FAB methods based on
FAB methods can be used in combination with abstinence or observation of fertility signs (e.g., cervical secretions, basal barrier methods during the fertile time. If barrier methods are body temperature) such as the Cervical Mucus Method, used, refer to Appendix G.
the Symptothermal Method, and the TwoDay Method.
No medical conditions become worse because of use of FAB • Calendar-based methods: FAB methods based on cal-
methods. In general, FAB methods can be used without con- endar calculations such as the Calendar Rhythm Method cern for health effects to persons who choose them. However, and the Standard Days Method.
a number of conditions make their use more complex. The • Acccept (A): There is no medical reason to deny the par-
existence of these conditions suggests that 1) use of these ticular FAB method to a woman in this circumstance.
methods should be delayed until the condition is corrected or • Caution (C): The method is normally provided in a
resolved or 2) persons using FAB methods will require special routine setting but with extra preparation and precau- counseling, and a more highly trained provider is generally tions. For FAB methods, this usually means that special necessary to ensure correct use.
counselling might be needed to ensure correct use of the Women with conditions that make pregnancy an unaccept- method by a woman in this circumstance.
able risk should be advised that FAB methods might not be • Delay (D): Use of this method should be delayed until the
appropriate for them because of the relatively higher typical-use condition is evaluated or corrected. Alternative temporary failure rates of these methods. FAB methods do not protect methods of contraception should be offered.
against sexually transmitted infections (STIs) or human immu- nodeficiency virus (HIV).
TABLE. Fertility awareness–based methods,*† including symptoms-based and calendar-based methods
Symptom-based Calendar-based
Personal Characteristics and Reproductive History
Clarification: FAB methods are not relevant during pregnancy.
Life stage
Clarification: Menstrual irregularities are common in postmenarche and perimeno-
pause and might complicate the use of FAB methods.
Comment: Use of FAB methods when breastfeeding might be less effective than
when not breastfeeding.
a. <6 wks postpartum Comment: Women who are primarily breastfeeding and are amenorrheic are
unlikely to have sufficient ovarian function to produce detectable fertility signs and hormonal changes during the first 6 months postpartum. However, the likelihood of resumption of fertility increases with time postpartum and with substitution of breast milk with other foods.
c. After menses begin Comment: When the woman notices fertility signs, particularly cervical secre-
tions, she can use a symptoms-based method. First postpartum menstrual cycles in breastfeeding women vary significantly in length. Return to regularity takes several cycles. When she has had at least 3 postpartum menses and her cycles are regular again, she can use a calendar-based method. When she has had at least 4 postpartum menses and her most recent cycle lasted 26–32 days, she can use the Standard Days Method. Before that time, a barrier method should be offered if the woman plans to use a FAB method later.
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TABLE. (Continued) Fertility awareness–based methods,*† including symptoms-based and calendar-based methods
Symptom-based Calendar-based
Postpartum (in nonbreastfeeding women)
Comment: Nonbreastfeeding women are not likely to have sufficient ovarian func-
tion to either require a FAB method or to have detectable fertility signs or hormonal changes before 4 weeks postpartum. Although the risk for pregnancy is low, a method appropriate for the postpartum period should be offered.
Comment: Nonbreastfeeding women are likely to have sufficient ovarian function
to produce detectable fertility signs and/or hormonal changes at this time; likelihood increases rapidly with time postpartum. Women can use calendar-based methods as soon as they have completed three postpartum menses. Methods appropriate for the postpartum period should be offered before that time.
Comment: Postabortion women are likely to have sufficient ovarian function to
produce detectable fertility signs and/or hormonal changes; likelihood increases with time postabortion. Women can start using calendar-based methods after they have had at least 1 postabortion menses (e.g., women who before this pregnancy had most cycles of 26–32 days can then use the Standard Days Method). Methods appropriate for the postabortion period should be offered before that time.
Reproductive Tract Infections and Disorders
Irregular vaginal bleeding
Comment: Presence of this condition makes FAB methods unreliable. Therefore,
barrier methods should be recommended until the bleeding pattern is compat- ible with proper method use. The condition should be evaluated and treated as Comment: Because vaginal discharge makes recognition of cervical secretions
difficult, the condition should be evaluated and treated if needed before providing methods based on cervical secretions.
Use of drugs that affect cycle regularity,
Comment: Use of certain mood-altering drugs such as lithium, tricyclic antidepres-
hormones, and/or fertility signs
sants, and antianxiety therapies, and certain antibiotics and anti-inflammatory drugs, might alter cycle regularity or affect fertility signs. The condition should be carefully evaluated and a barrier method offered until the degree of effect has been determined or the drug is no longer being used.
Diseases that elevate body temperature
a. Chronic diseases Comment: Elevated temperature levels might make basal body temperature dif-
ficult to interpret but have no effect on cervical secretions. Thus, use of a method b. Acute diseases that relies on temperature should be delayed until the acute febrile disease abates. Temperature-based methods are not appropriate for women with chronically elevat- ed temperatures. In addition, some chronic diseases interfere with cycle regularity, making calendar-based methods difficult to interpret.
* Abbreviations: FAB = fertility awareness–based; A = accept; C = caution; D = delay; STI = sexually transmitted infection; HIV = human immunodeficiency infection.
† Fertility awareness–based methods do not protect against STI/HIV. If risk exists for STI/HIV (including during pregnancy or postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive method. Consistent and correct use of the male latex condom reduces the risk for STIs and HIV transmission.
Early Release
Appendix I
Lactational Amenorrhea Method
The Bel agio Consensus provided the scientific basis for ment feeding is affordable, feasible, acceptable, sustainable, defining the conditions under which breastfeeding can be and safe, breastfeeding for women with HIV is not recom- used safely and effectively for birth-spacing purposes, and programmatic guidelines were developed for use of lacta- tional amenorrhea in family planning (1,2). These guidelines Other Medical Conditions
include the following three criteria, all of which must be met The American Academy of Pediatrics also recommends to ensure adequate protection from an unplanned pregnancy: against breastfeeding for women with active untreated tuber- 1) amenorrhea; 2) fully or nearly fully breastfeeding, and 3) culosis disease, who are positive for human T-cell lymphotropic <6 months postpartum.
virus types I or II, or who have herpes simplex lesions on a The main indications for breastfeeding are to provide an ideal breast (infant can feed from the other breast). In addition, food for the infant and protect against disease. No medical infants with classic galactosemia should not breastfeed (4).
conditions exist for which use of the lactational amenorrhea Medication Used during Breastfeeding
method for contraception is restricted. However, breastfeed- ing might not be recommended for women or infants with To protect infant health, the American Academy of Pediatrics certain conditions. does not recommend breastfeeding for women receiving certain Women with conditions that make pregnancy an unac- drugs, including diagnostic or therapeutic radioactive isotopes ceptable risk should be advised that the lactational amenor- or exposure to radioactive materials, antimetabolites or chemo- rhea method might not be appropriate for them because of therapeutic agents, and current use of drugs of abuse (4).
its relatively higher typical-use failure rates. The lactational amenorrhea method does not protect against sexually trans- 1. Kennedy KI, Rivera R, McNeilly AS. Consensus statement on the use of breastfeeding as a family planning method. Contraception mitted infections (STIs) and human immunodeficiency virus (HIV). If risk exists for STI/HIV (including during pregnancy 2. Labbok M, Cooney K, Coly S. Guidelines: breastfeeding, family plan- or postpartum), the correct and consistent use of condoms ning, and the Lactational Amenorrhea Method-LAM. Washington, DC: Institute for Reproductive Health; 1994. is recommended, either alone or with another contraceptive 3. Perinatal HIV Guidelines Working Group. Public Health Service Task method. Consistent and correct use of the male latex condom Force recommendations for use of antiretroviral drugs in pregnant HIV- reduces the risk for STIs and HIV transmission. infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Rockville, MD: Public Health Service Task Force; 2009.
4. Gartner LM, Morton J, Lawrence RA, et al. Breastfeeding and the use of HIV can be transmitted from mother to infant through human milk. Pediatrics 2005;115:496–506.
breastfeeding. Therefore, in the United States, where replace- Early Release
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Appendix J
Coitus Interruptus (Withdrawal)
Coitus interruptus (CI), also known as withdrawal, is a tra- Some benefits of CI are that the method, if used correctly, ditional family planning method in which the man completely does not affect breastfeeding and is always available for primary removes his penis from the vagina, and away from the external use or use as a back-up method. In addition, CI involves no genitalia of the female partner, before he ejaculates. CI prevents economic cost or use of chemicals. CI has no directly associated sperm from entering the woman's vagina, thereby preventing health risks. CI does not protect against sexually transmitted contact between spermatozoa and the ovum.
infections (STIs) and human immunodeficiency virus (HIV). This method might be appropriate for couples If risk exists for STI/HIV (including during pregnancy or • who are highly motivated and able to use this method postpartum), the correct and consistent use of condoms is recommended, either alone or with another contraceptive • with religious or philosophical reasons for not using other method. Consistent and correct use of the male latex condom methods of contraception; reduces the risk for STIs and HIV transmission.
• who need contraception immediately and have entered CI is unforgiving of incorrect use, and its effectiveness into a sexual act without alternative methods available; depends on the willingness and ability of the couple to use • who need a temporary method while awaiting the start of withdrawal with every act of intercourse. Women with con- another method; or ditions that make pregnancy an unacceptable risk should be • who have intercourse infrequently.
advised that CI might not be appropriate for them because of its relatively higher typical-use failure rates.
Early Release
Appendix K
Female and Male Sterilization
Tubal sterilization for women and vasectomy for men are sterilization remain satisfied with their decision. However, a permanent, safe, and highly effective methods of contraception. smal proportion of women regret this decision (1%–26% from In general, no medical conditions would absolutely restrict different studies, with higher rates of regret reported by women a person's eligibility for sterilization (with the exception of who were younger at sterilization) (1,2). Regret among men known al ergy or hypersensitivity to any materials used to about vasectomy has been reported to be approximately 5% complete the sterilization method). However, certain condi- (3), similar to the proportion of women who report regretting tions place a woman at high surgical risk; in these cases, careful their husbands' vasectomy (6%) (4). Therefore, al persons consideration should be given to the risks and benefits of other should be appropriately counseled about the permanency of acceptable alternatives, including long-acting, highly effective, sterilization and the availability of highly effective, reversible reversible methods and vasectomy. Female and male steriliza- methods of contraception.
tion do not protect against sexual y transmitted infections (STIs) or human immunodeficiency virus (HIV). If risk exists 1. Peterson HB. Sterilization. Obstet Gynecol 2008;111:189–203.
for STI/HIV (including during pregnancy or postpartum), the 2. Hil is SD, Marchbanks PA, Tylor LR, Peterson HB. Poststerilization regret: correct and consistent use of condoms is recommended, either findings from the United States Collaborative Review of Sterilization. Obstet Gynecol 1999;93:889–95.
alone or with another contraceptive method. Consistent and 3. Ehn BE, Liljestrand J. A long-term follow-up of 108 vasectomized correct use of the male latex condom reduces the risk for STIs men. Good counselling routines are important. Scand J Urol Nephrol and HIV transmission.
4. Jamieson DJ, Kaufman SC, Costello C, et al. A comparison of women's Because these methods are intended to be irreversible, per- regret after vasectomy versus tubal sterilization. Obstet Gynecol sons who choose sterilization should be certain that they want to prevent pregnancy permanently. Most persons who choose Early Release
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Appendix L
Summary of Classifications for Hormonal Contraceptive Methods and
Health-care providers can use the summary table as a quick classifications across these methods. See the full appendix for reference guide to the classifications for hormonal contracep- each method for clarifications to the numeric categories, as well tive methods and intrauterine contraception and to compare as for summaries of the evidence and additional comments.
BOX. Categories for Classifying Hormonal Contraceptives and IUDs
1 = A condition for which there is no restriction for the use of the contraceptive method.
2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.
3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.
4 = A condition that represents an unacceptable health risk if the contraceptive method is used.
TABLE. Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
Personal Characteristics and Reproductive History
Not applicable† Not applicable† Not applicable† Not applicable† a. <1 mo postpartum b. 1 mo to <6 mos c. ≥6 mos postpartum Postpartum
(nonbreastfeeding women) Postpartum (breastfeeding or
nonbreastfeeding women, including post-Cesarean section) a. <10 min after delivery of the b. 10 min after delivery of the pla- centa to <4 wks d. Puerperal sepsis a. First trimester b. Second trimester c. Immediate postseptic abortion Past ectopic pregnancy
History of pelvic surgery (see post-
partum, including Cesarean section) a. Age <35 yrs i. <15 Cigarettes/day ii. ≥15 Cigarettes/day Early Release
TABLE. (Continued) Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
a. ≥30 kg/m2 BMI b. Menarche to <18 yrs and History of bariatric surgery§
a. Restrictive procedures: decrease storage capacity of the stomach (vertical banded gastroplasty, lap- aroscopic adjustable gastric band, laparoscopic sleeve gastrectomy) b. Malabsorptive procedures: decrease absorption of nutrients and calories by shortening the functional length of the small in- testine (Roux-en-Y gastric bypass, Multiple risk factors for arterial
cardiovascular disease (such as
older age, smoking, diabetes, and a. Adequately controlled b. Elevated blood pressure levels (properly taken measurements) i. Systolic 140–159 mm Hg or diastolic 90–99 mm Hg ii. Systolic ≥160 mm Hg or diastolic ≥100 mm Hg§ c. Vascular disease History of high blood pressure dur-
ing pregnancy (where current blood
pressure is measurable and normal) Deep venous thrombosis (DVT)/
pulmonary embolism (PE)
a. History of DVT/PE, not on anticoagulant therapy i. Higher risk for recurrent DVT/ PE (≥1 risk factors) • History of estrogen- associated DVT/PE • Pregnancy-associated • Idiopathic DVT/PE • Known thrombophilia, including antiphospholipid • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/PE (no risk factors) c. DVT/PE and established on anticoagulant therapy for at least 3 mos i. Higher risk for recurrent DVT/ PE (≥1 risk factors) • Known thrombophilia, including antiphospholipid • Active cancer (metastatic, on therapy, or within 6 mos after clinical remission), excluding non-melanoma skin cancer • History of recurrent DVT/PE ii. Lower risk for recurrent DVT/ PE (no risk factors) Early Release
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TABLE. (Continued) Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
d. Family history (first-degree i. With prolonged immobilization ii. Without prolonged f. Minor surgery without Known thrombogenic mutations§
(e.g. factor V Leiden; prothrombin mutation; protein S, protein C, and Superficial venous thrombosis
a. Varicose veins b. Superficial thrombophlebitis Current and history of ischemic
Initiation Continuation Initiation Continuation Initiation Continuation Stroke§ (history of cerebrovascular
Initiation Continuation Initiation Continuation Known hyperlipidemias
Valvular heart disease
b. Complicated§ (pulmonary hyper- tension, risk for atrial fibrillation, history of subacute bacterial a. Normal or mildly impaired car- diac function (New York Heart Association Functional Class I or II: patients with no limitation of activities or patients with slight, mild limitation of activity) (1) i. <6 mos b. Moderately or severely impaired cardiac function (New York Heart Association Functional Class III or IV: patients with marked limitation of activity or patients who should be at complete rest) (1) Systemic lupus erythematosus§
Initiation Continuation Initiation Continuation a. Positive (or unknown) antiphos- pholipid antibodies b. Severe thrombocytopenia c. Immunosuppressive treatment d. None of the above Initiation Continuation Initiation Continuation a. On immunosuppressive therapy b. Not on immunosuppressive Initiation Continuation Initiation Continuation Initiation Continuation Initiation Continuation Initiation Continuation a. Non-migrainous (mild or severe) • Age <35 yrs • Age ≥35 yrs ii. With aura (at any age) If on treatment, see Drug Interactions section below Early Release
TABLE. (Continued) Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
Reproductive Tract Infections and Disorders
Vaginal bleeding patterns
Initiation Continuation a. Irregular pattern without heavy b. Heavy or prolonged bleeding (includes regular and irregular Unexplained vaginal bleeding (sus-
Initiation Continuation Initiation Continuation picious for serious condition) Before evaluation Benign ovarian tumors (including
Gestational trophoblastic disease
a. Decreasing or undetectable ß-hCG b. Persistently elevated ß-hCG levels or malignant disease§ Cervical intraepithelial neoplasia
Cervical cancer (awaiting treatment)
Initiation Continuation Initiation Continuation a. Undiagnosed mass b. Benign breast disease c. Family history of cancer d. Breast cancer§ ii. Past and no evidence of current disease for 5 yrs Initiation Continuation Initiation Continuation a. Distorted uterine cavity (any con- genital or acquired uterine abnor- mality distorting the uterine cavity in a manner that is incompatible with IUD insertion) b. Other abnormalities (including cervical stenosis or cervical lacera- tions) not distorting the uterine cavity or interfering with IUD Pelvic inflammatory disease (PID)
a. Past PID (assuming no current risk Initiation Continuation Initiation Continuation i. With subsequent pregnancy ii. Without subsequent pregnancy Early Release
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TABLE. (Continued) Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
Initiation Continuation Initiation Continuation a. Current purulent cervicitis or chla- mydial infection or gonorrhea b. Other STIs (excluding HIV and c. Vaginitis (including Trichomonas vaginalis and bacterial vaginosis) d. Increased risk for STIs Initiation Continuation Initiation Continuation High risk for HIV
Clinically well on ARV therapy If on treatment, see Drug Interactions section below b. Fibrosis of the liver (if severe, Initiation Continuation Initiation Continuation If on treatment, see Drug Interactions section below a. History of gestational disease b. Nonvascular disease i. Noninsulin-dependent ii. Insulin-dependent§ d. Other vascular disease or diabetes of >20 yrs' duration§ Inflammatory bowel disease (IBD)
(ulcerative colitis, Crohn disease) i. Treated by cholecystectomy ii. Medically treated History of cholestasis
a. Pregnancy-related b. Past COC-related Initiation Continuation a. Acute or flare a. Mild (compensated) b. Severe§ (decompensated) Early Release
TABLE. (Continued) Summary of classifications for hormonal contraceptive methods and intrauterine devices*
Condition
Liver tumors
i. Focal nodular hyperplasia ii. Hepatocellular adenoma§ b. Malignant§ (hepatoma) Sickle cell disease§
Solid Organ Transplantation
Solid organ transplantation§
Initiation Continuation Initiation Continuation a. Complicated: graft failure (acute or chronic), rejection, cardiac allograft Antiretroviral therapy (see appendix M)
Initiation Continuation Initiation Continuation a. Nucleoside reverse transcriptase inhibitors (NRTIs) b. Non-nucleoside reverse tran- scriptase inhibitors (NNRTIs) c. Ritonavir-boosted protease a. Certain anticonvulsants (phe- nytoin, carbamazepine, barbi- turates, primidone, topiramate, a. Broad-spectrum antibiotics c. Antiparasitics d. Rifampicin or rifabutin therapy * Abbreviations: COC = combined oral contraceptive; P = combined hormonal contraceptive patch; R = combined hormonal vaginal ring; POP = progestin-only pill; DMPA = depot medroxyprogesterone acetate; IUD = intrauterine device; LNG-IUD = levonorgestrel-releasing IUD; Cu-IUD = copper IUD; BMI = body mass index; DVT = deep venous thrombo- sis; PE = pulmonary embolism; hCG, = human chorionic gonadotropin; PID = pelvic inflammatory disease; STI = sexually transmitted infection; HIV = human immunodeficiency virus; AIDS = acquired immunodeficiency syndrome; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase.
† Consult the appendix for this contraceptive method for a clarification to this classification. § Condition that exposes a woman to increased risk as a result of unintended pregnancy.
1. The Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Little, Brown & Co.; 1994.
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Appendix M
Summary of Evidence Regarding Potential Drug Interactions between
Hormonal Contraception and Antiretroviral therapies
Limited data from small, mostly unpublished studies sug- Tables 1 and 2 summarize the evidence available about drug gest that some antiretroviral (ARV) therapies might alter the interactions between ARV therapies and hormonal contra- pharmacokinetics of combined oral contraceptives (COCs). ceptives. For up-to-date, detailed information about human Few studies have measured clinical outcomes. However, con- immunodeficiency virus (HIV) drug interactions, the following traceptive steroid levels in the blood decrease substantially with resources might be helpful: ritonavir-boosted protease inhibitors. Such decreases have the • Guidelines for the Use of Antiretroviral Agents in HIV- potential to compromise contraceptive effectiveness. Some of 1-Infected Adults and Adolescents from the DHHS the interactions between contraceptives and ARVs also have Panel on Antiretroviral Guidelines for Adults and led to increased ARV toxicity. For smaller effects that occur Adolescents. Available with non-nucleoside reverse transcriptase inhibitors, clinical significance is unknown, especially because studies have not • HIV Drug Interactions website, University of Liverpool, examined steady-state levels of contraceptive hormones. No UK. Available at www.hiv-druginteractions.org.
clinically significant interactions have been reported between contraceptive hormones and nucleoside reverse transcriptase TABLE 1. Drug interactions between COCs and ARV drugs*
ARV
Nucleoside reverse transcriptase inhibitors (NRTIs)
Tenofovir disaproxil fumarate
EE ↔, NGM ↔ (1) Tenofovir ↔ (1) Zidovudine ↔ (2) No change in viral load or CD4+ (2) Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz
EE ↑ (3), EE ↔ (4), NGM ↓ (4), LNG ↓ (4) Efavirenz ↔ (3,4) Pregnancy rate 2.6/100 woman-years in 1 study in which up to 80% used hormonal contraceptives (35% used COC) (5) EE ↔, NET ↔ (6) Etravirine ↑ (6)Concurrent administration, generally safe and well tolerated EE ↔, NET ↔ (7) Nevirapine ↔ (7) Protease inhibitors and ritonavir-boosted protease inhibitors
Atazanavir/ritonavir
EE ↑, NET ↑ (8) EE ↓, NET ↔ (9) Darunavir ↔ (9) EE ↓ (10,11), NET ↓ (11) Amprenavir ↔, ritonavir ↑, Elevated liver transaminases (10) EE ↔, NET ↔ (12) EE ↓, NET ↔ (13) EE ↓, NET ↔ (14) Saquinavir ↔ (15,16) EE↓ (17) ↑ Skin and musculoskeletal adverse events; possible drug hypersensitivity reaction (17) * Abbreviations: COC = combined oral contraceptive; ARV = antiretroviral; EE = ethinyl estradiol; NGM = norgestimate; NNRTI = non-nucleoside reverse transcriptase inhibitor; LNG = levonorgestrel; NET = norethindrone.
† ↔, no change or change ≤30%; ↑, increase >30%; ↓, decrease >30%.
§ Saquinavir and indinavir are commonly given boosted by ritonavir, but there are no data on contraceptive interactions with the boosted regimens.
Early Release
TABLE 2. Drug interactions between DMPA and ARV drugs*
Nucleoside reverse transcriptase inhibitors (NRTIs)
Zidovudine ↔ (2) No change in viral load Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
MPA ↔ (18,19) Efavirenz ↔ (18) No ovulations during 3 cycles(18,19) No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20) Pregnancy rate 2.6/100 woman-years in 1 study where up to 80% used hormonal contraceptives (65% used MPA ↔ (18) Nevirapine ↑ (18) No ovulations during 3 cycles(18) No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20) Protease inhibitors and ritonavir-boosted protease inhibitors
MPA ↔ (18) Nelfinavir ↔ (18) No change in viral load or CD4+, no grade 3- or 4-related adverse events§ (20) * Abbreviations: DMPA = depot medroxyprogesterone acetate; ARV = antiretroviral; NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase; MPA = medroxyprogesterone acetate; POI = progestin-only injectables.
† ↔, no change or change ≤30%; ↑, increase > 30%.
§ The trial applied the standardized National Institutes of Health Division of AIDS Table for Grading Severity of Adult and Pediatric Adverse Events, 2004 Grade 3 events are clas- sified as severe. Severe events are defined as symptoms that limit activity or might require some assistance; require medical intervention or therapy; and might require hospitalization. Grade 4 events are classified as life threatening. Life-threatening events include symptoms that result in extreme limitation of activity and require substantial assistance; require substantial medical intervention and therapy; and probably require hospitalization or hospice.
8. Zhang J, Chung E, Eley T et al. Effect of atazanavir/ritonavir on the 1. Kearney BP, Isaacson E, Sayre J, Cheng AK. Tenofovir DF and oral pharmacokinetics of ethinyl estradiol and 17-deactyl-norgestimate in contraceptives: lack of a pharmacokinetic drug interaction [Abstract healthy female subjects [Abstract A-1415]. In: Program and abstracts A-1618]. In: Program and abstracts of the 43rd Interscience Conference on of the 47th Interscience Conference on Antimicrobial Agents and Antimicrobial Agents and Chemotherapy, Chicago, IL, September 14–17, Chemotherapy, Chicago, IL, September 17–20, 2007. Washington, 2003. Washington, DC: American Society for Microbiology; 2003.
DC: American Society for Microbiology; 2009.
2. Aweeka FT, Rosenkranz SL, Segal Y, et al. The impact of sex and con- 9. Sekar V, Lefebvre E S-GSeal. Pharacokinetic interaction between traceptive therapy on the plasma and intracellular pharmacokinetics of nevirapine and ethinyl estradiol, norethindrone, and TMC114, a new zidovudine. AIDS 2006;20:1833–41.
protease inhibitor [Abstract A-368]. In: Program and abstracts of the 46th 3. Joshi AS, Fiske WD, Benedek IH, et al. Lack of a pharmacokinetic Interscience Conference on Antimicrobial Agents and Chemotherapy, interaction between efavirenz (DMP 266) and ethinyl estradiol in healthy San Francisco, CA, September 27–30, 2006. Washington, DC: American female volunteers [Abstract 348]. 5th Conference on Retroviruses and Society for Microbiology; 2009.
Opportunistic Infections, Chicago, IL, February 1–5, 1998.
10. Glaxo Smith Kline. Prescription medicines. Lexiva (fosamprenavir 4. Sevinsky H, Eley T, He B, et al. Effect of efavirenz on the pharacokinetics calcium). Glaxo Smith Kline 2009. Available from of ethinyl estradiol and norgestimate in healthy female subjects [Abstract . Accessed March 15, 2010.
A958]. In: Program and abstracts of the 48th Interscience Conference on 11. Glaxo Smith Kline. Study APV10020. A phase I, open label, two period, Antimicrobial Agents and Chemotherapy, Washington, DC, October single-sequence, drug-drug interaction study comparing steady-state 25–28, 2008. Washington, DC: American Society for Microbiology; plasma ethinyl estradiol and norethisterone pharmacokinetics fol owing administration of brevinor for 21 days with and without fosamprenavir 5. Danel C, Moh R, Anzian A, et al. Tolerance and acceptability of an 700 mg twice daily (BID) and ritonavir 100 mg (BID) for 21 days in efavirenz-based regimen in 740 adults (predominantly women) in West healthy adult female subjects. Glaxo Smith Kline 2009. Available from Africa. J Acquir Immune Defic Syndr 2006;42:29–35.
6. Scholler-Gyure M, Debroye C, Aharchi F, et al. No clinically relevant March 15, 2010.
effect of TMC125 on the pharmacokinetics of oral contraceptives. 8th 12. Merck & Company. Indinavir patient prescribing information. Merck International Congress on Drug Therapy in HIV Infection, Glasgow, & Company 2009. Available fr UK, November 12–16, 2006.
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7. Mildvan D, Yarrish R, Marshak A, et al. Pharmacokinetic interaction 13. Abbott Laboratories. Lopinavir and ritonavir prescribing information, between nevirapine and ethinyl estradiol/norethindrone when admin- 2009. Abbott Laboratories 2009. Available from istered concurrently to HIV-infected women. J Acquir Immune Defic . Accessed March 15, 2010.
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15. Mayer K, Poblete R, Hathaway B et al. Efficacy, effect of oral contra- 18. Cohn SE, Park JG, Watts DH, et al. Depo-medroxyprogesterone in ceptives, and adherence in HIV infected women receiving Fortovase women on antiretroviral therapy: effective contraception and lack of clini- (Saquinavir) soft gel capsule (SQV-SGC; FTV) thrice (TID) and twice cally significant interactions. Clin Pharmacol Ther 2007;81:222–7.
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medroxyprogesterone acetate among HIV-infected women on antiret- 17. Food and Drug Administration. Highlights of prescribing information. Aptivus roviral therapy: ACTG A5093. Contraception 2008;77:84–90.
(Tipranavir) Capsules. USFDA 2009. Available fr Early Release
Abbreviations and Acronyms
acquired immunodeficiency syndrome bone mineral density Centers for Disease Control and Prevention combined hormonal contraceptive coitus interruptus combined oral contraceptive copper intrauterine device depot medroxyprogesterone acetate deep venous thrombosis emergency contraceptive pills ethinyl estradiol emergency intrauterine device fertility awareness–based methods human chorionic gonadotropin high-density lipoprotein human immunodeficiency virus human papillomavirus inflammatory bowel disease intrauterine system intrauterine device levonorgestrel-releasing intrauterine device Medical Eligibility Criteria norethisterone enantate non-nucleoside reverse transcriptase inhibitor nucleoside reverse transcriptase inhibitor combined hormonal contraceptive patch pulmonary embolism pelvic inflammatory disease progestin-only pill combined hormonal vaginal ring systemic lupus erythematosus sexually transmitted infection venous thromboembolism World Health Organization Early Release
May 28, 2010
U.S. Medical Eligibility Criteria for Contraceptive Use, 2010
Atlanta, GA, February 17–19, 2009
Chairpersons: Herbert B. Peterson, MD, University of North Carolina, Chapel Hill, North Carolina; Kathryn M. Curtis, PhD, Centers for Disease Control
and Prevention, Atlanta, Georgia.
CDC Steering Committee: Kathryn M. Curtis, PhD (Chair), Denise Jamieson, MD, John Lehnherr, Polly Marchbanks, PhD, Centers for Disease Control
and Prevention, Atlanta, Georgia.
Systematic Review Authors and Presenters: Sherry Farr, PhD, Suzanne Gaventa Folger, PhD, Melissa Paulen, MPH, Naomi Tepper, MD, Maura Whiteman,
PhD, Lauren Zapata, PhD, Centers for Disease Control and Prevention, Atlanta, Georgia; Kelly Culwell, MD, Nathalie Kapp, MD, World Health Organization, Geneva, Switzerland; Catherine Cansino, MD, Johns Hopkins Bayview Medical Center, Baltimore, Maryland.
Invited Participants: Abbey Berenson, MD, University of Texas Medical Branch, Nassau Bay, Texas; Paul Blumenthal, MD, Stanford University, Palo Alto,
California (not able to attend); Willard Cates, Jr., MD, Family Health International, Research Triangle Park, North Carolina (not able to attend); Mitchell Creinin, MD, University of Pittsburgh, Pittsburgh, Pennsylvania; Vanessa Cullins, MD, Planned Parenthood Federation of America, New York, New York; Philip Darney, MD, University of California, San Francisco, California; Jennifer Dietrich, MD, Baylor College of Medicine, Houston, Texas; Linda Dominguez, Southwest Women's Health, Albuquerque, New Mexico; Melissa Gilliam, MD, The University of Chicago, Chicago, Illinois; Marji Gold, MD, Albert Einstein College of Medicine, Bronx, New York; Alisa Goldberg, MD, Brigham and Women's Hospital and Planned Parenthood of Massachusetts, Boston, Massachusetts; David Grimes, MD, Family Health International, Research Triangle Park, North Carolina (not able to attend); Robert Hatcher, MD, Emory University, Atlanta, Georgia; Stephen Heartwell, DrPH, Susan Thompson Buffett Foundation, Omaha, Nebraska; Andrew Kaunitz, MD, University of Florida, Jacksonville, Florida; Uta Landy, PhD, University of California, San Francisco, California (not able to attend); Hal Lawrence, MD, American College of Obstetricians and Gynecologists, Washington, DC; Ruth Lawrence, MD, American Academy of Pediatrics and University of Rochester, Rochester, New York; Laura MacIsaac, MD, Albert Einstein School of Medicine, New York, New York; Trent MacKay, MD, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (not able to attend); Daniel Mishell, Jr, MD, University of Southern California, Los Angeles, California; Mary Mitchell, American College of Obstetricians and Gynecologists, Washington, DC; Susan Moskosky, MS, US Department of Health and Human Services, Rockville, Maryland; Patricia Murphy, DrPH, University of Utah, Salt Lake City, Utah; Kavita Nanda, MD, Family Health International, Research Triangle Park, North Carolina; Jeffrey Peipert, MD, Washington University, St. Louis, Missouri; Michael Policar, MD, University of California, San Francisco, California; Robert Rebar, MD, American Society of Reproductive Medicine, Birmingham, Alabama; Pablo Rodriquez, MD, Providence, Rhode Island (not able to attend); John Santelli, MD, Columbia University, New York, New York (not able to attend); Sharon Schnare, MSN, University of Washington, Seattle, Washington; David Soper, MD, University of South Carolina, Charleston, South Carolina; Lisa Soule, MD, Food and Drug Administration, Silver Spring, Maryland; James Trussell, PhD, Princeton University, Princeton, New Jersey; Carolyn Westhoff, MD, Columbia University, New York, New York (not able to attend); Susan Wysocki, National Association of Nurse Practitioners in Women's Health, Washington, DC; Mimi Zieman, MD, Emory University, Atlanta, Georgia.
Consultants: Wendy Book, MD, Emory University, Atlanta, Georgia; Shinya Ito, Hospital for Sick Children, Toronto, Canada; Beth Jonas, MD, University
of North Carolina, Chapel Hill, North Carolina; Miriam Labbok, MD, University of North Carolina, Chapel Hill, North Carolina; Frederick Naftolin, MD, New York University, New York, New York; Lubna Pal, Yale University, New Haven, Connecticut; Robin Rutherford, MD, Emory University, Atlanta, Georgia; Roshan Shrestha, MD, Piedmont Hospital, Atlanta, Georgia; Kimberley Steele, MD, Johns Hopkins University, Baltimore, Maryland; Michael Streiff, MD, Johns Hopkins University, Baltimore, Maryland; Christine Wagner, PhD, University of Albany, Albany, New York; Joan Walker, MD, University of Oklahoma, Oklahoma City, Oklahoma.
CDC Attendees: Janet Collins, PhD, Susan Hillis, PhD, Dmitry Kissin MD, Sam Posner, PhD, Natalya Revzina, MD, Cheryl Robbins, PhD, Lee Warner,
PhD.
This work was conducted within the Women's Health and Fertility Branch (Maurizio Macaluso, Branch Chief), in the Division of Reproductive Health (John Lehnherr, Acting Director), National Center for Chronic Disease Prevention and Health Promotion (Ursula Bauer, Director).

Source: http://p3georgia.org/wp-content/uploads/2016/06/rr59e0528.pdf